New Explanations for Evolution of Alzheimer’s Disease (AD): The Association between Brain neuroanatomy, Brain Pathology and AD Biomarkers – Orientation and Attention are affected by the roles of Temporo-parietal junction (TPJ), Ventral attentional control network, Theory of mind, Inferior parietal cortex
Reporter and Curator: Aviva Lev-Ari, PhD, RN
UPDATED on 3/2/2020
Blood test method may predict Alzheimer’s protein deposits in brain
NIH-funded study reports advance in blood-based detection of ptau181, a biomarker of Alzheimer’s disease.
On 2/27/2020 I attended an AFHU event with Prof. Shahar Arzi, MD, PhD as Speaker. The main argument was the Title of this curation: AD biomarkers of Amyloid and Tau deposits are found in the TPJ areas of the Brain where Attention, Theory of Mind and Empathy functions occur. Early detection of AD reveals symptoms of effects on Orientation and Attention. Application of Machine Learning (ML) on Brain imaging data allows for prediction of AD disease progression.
As an alternative or complementary Explanation we present “The multiplex model of the genetics of Alzheimer’s disease”
- The multiplex model reflects the combination of some, or all, of these model components (genetic and environmental), in a tissue-specific manner, to trigger or sustain a disease cascade, which ultimately results in the cell and synaptic loss observed in AD.
The Loss of Orientation and Attention are an outcome of Brain neuroanatomy, Brain Pathology and AD Biomarkers
Dr. Shahar Arzy got his MD and MSc in neuroscience at the Hebrew University and PhD in neuroscience from the Swiss institute of Technology at the University of Geneva. He specialized in Neurology at Hadassah with subspecialty in cognitive neurology and epilepsy at Geneva University Hospital.
He now directs the Neuropsychiatry Lab at the Hebrew University and runs the neuropsychiatry clinic (with Dr. R. Eitan) and the epilepsy center (with Dr. D. Ekstein) in Hadassah Medical Center.
Dr. Arzy is a senior lecturer at the faculty of medicine, The Edmond And Lily Safra Brain Center and the Cognitive Science Program at the Hebrew University of Jerusalem.
Research Interests: Computational Neuropsychiatry Lab: Our lab of Computational Neuropsychiatry aims to bridge the gap between clinical practice and research, neurology, psychiatry, physics and psychology in order to re-formulate our understanding of the human self and its pathologies. To this aim we use newly developed computational methods (machine-learning algorithms, classifiers, network-approach and spectral analysis) applied directly on patients’ data (3T/7T fMRI, intracranial brain recordings, EEG, ECT), particularly tailored to improve clinical management and scientific understanding of neuropsychiatric disorders. The Neuropsychiatry Lab is located within the Department of Neurology and has a close collaboration with the Departments of Psychiatry, Neuroradiology and Neurosurgery, in order to develop approaches to address specific medical needs of neuropsychiatric patients and clinicians. Our main interests involve cortex-related functional conditions including epilepsy, neurodegenerative diseases, conversive and dissociative disorders, amnesias, disorientation states and different cognitive disturbances and misperceptions. By combining direct clinical involvement and cutting-edge computational methods we are able to challenge the customary context of the human “self” and to reframe neuropsychiatry, and at the same time to develop effective patient-tailored clinical tools to diagnose, monitor and treat these disorders.
SOURCE
https://scholars.huji.ac.il/jbc/people/dr-shahar-arzy
Position(s):Associate Medical Director of Clinical Trials, Center for Alzheimer’s Research and Treatment, Brigham and Women’s HospitalAssociate Professor of Neurology, Harvard Medical SchoolAffiliation(s):Brigham and Women’s Hospital; Massachusetts General Hospital; Harvard Medical SchoolTelephone:(617) 732-8085Interests:I have a long-standing interest in clinical-pathologic and imaging correlates in Alzheimer’s disease. Most recently, I have been using PET imaging to assess the relationship between apathy, executive function and instrumental activities of daily living, in vivo amyloid deposition (PiB PET) and synaptic integrity (FDG PET) in mild cognitive impairment and mild Alzheimer’s disease.
My other main research interest and involvement is in clinical trials for the treatment of Alzheimer’s disease.
More Information: Marshall Profile
Biography & Research:During my medical education at the Boston University School of Medicine, medical internship/neurology residency at the University of Pittsburgh and dementia fellowship at the University of California, Los Angeles, I developed both my clinical and research interests in Alzheimer’s disease. Along the way, I have collaborated with multiple investigators who encouraged and nurtured my drive to better understand this devastating disorder and find effective treatments.
I currently work as a behavioral neurologist at the Brigham and Women’s Hospital and the Massachusetts General Hospital, focusing on clinical trials and neuroimaging biomarkers in Alzheimer’s disease and its precursor stages.
Selected Publications:
Marshall GA, Kaufer DI, Lopez OL, Rao GR, Hamilton RL, DeKosky ST. Right Proscubiculum Amyloid Plaque Density Correlates with Anosognosia in Alzheimer’s Disease. J Neurol Neurosurg Psychiatry 2004; 75: 1396-1400. [PMCID: 1738763].
Marshall GA, Hendrickson R, Kaufer DI, Ivanco LS, Bohnen NI. Cognitive Correlates of Brain MRI Subcortical Signal Hyperintensities in Non-Demented Elderly. Int J Geriatr Psychiatry 2006; 21: 32-35.
Marshall GA, Fairbanks LA, Tekin S, Vinters HV, Cummings JL. Neuropathologic Correlates of Activities of Daily Living in Alzheimer’s Disease. Alzheimer Dis Assoc Disord 2006; 20: 56-59.
Marshall GA, Fairbanks LA, Tekin S, Vinters HV, Cummings JL. Neuropathologic Correlates of Apathy in Alzheimer’s Disease. Dement Geriatr Cogn Disord 2006; 21: 144-147.
Marshall GA, Shchelchkov E, Kaufer DI, Ivanco LS, Bohnen NI. White Matter Hyperintensities and Cortical Acetylcholinesterase Activity in Parkinsonian Dementia. Act Neurol Scand 2006; 113: 87-91.
Marshall GA, Monserratt L, Harwood D, Mandelkern M, Cummings JL, Sultzer DL. Positron Emission Tomography Metabolic Correlates of Apathy in Alzheimer’s Disease. Arch Neurol 2007; 64: 1015-1020.
Sperling RA, Laviolette PS, OíKeefe K, OíBrien J, Rentz DM, Pihlajamaki M, Marshall G, Hyman BT, Selkoe DJ, Hedden T, Buckner RL, Becker JA, Johnson KA. Amyloid Deposition is associated with Impaired Default Network Function in Older Persons Without Dementia. Neuron 2009; 63: 178-188. [PMCID: 2738994].
Becker JA, Hedden T, Carmasin J, Maye J, Rentz DM, Putcha D, Fischl B, Greve D, Marshall GA, Salloway S, Marks D, Buckner RL, Sperling RA, Johnson KA. Amyloid-Beta Associated Cortical Thinning in Clinically Normal Elderly. Ann Neurol 2011; 69: 1032-1042. [PMCID: 3117980].
Marshall GA, Rentz DM, Frey MT, Locascio JJ, Johnson KA, Sperling RA, Alzheimerís Disease Neuroimaging Initiative. Executive Function and Instrumental Activities of Daily Living in Mild Cognitive Impairment and Alzheimerís Disease. Alzheimers Dementia 2011; 7: 300-308. [PMCID: 3096844].
Marshall GA, Olson LE, Frey MT, Maye J, Becker JA, Rentz DM, Sperling RA, Johnson KA, Alzheimerís Disease Neuroimaging Initiative. Instrumental Activities of Daily Living Impairment is associated with Increased Amyloid Burden. Dement Geriatr Cogn Disord 2011; 31: 443-450. [PMCID: 3150869].
More publications may be accessed at www.ncbi.nlm.nih.gov/sites/entrez?db=pubmed
SOURCE
https://www.madrc.org/members/10908
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Perception and Multisensory Integration in Neurological Patients Using fMRI
https://clinicaltrials.gov/ct2/show/NCT01469858
02/11/2017
Soc-Cog Colloq – Shahar Arzi
14:00
Wechsler Orientation and its role in Alzheimer’s disease: Mental-orientation is the cognitive function that manages the relationship between the individual and the environment in time (events), space (places) and person (people), as based on a distinct brain system. Observing the clinical similarities between mental-orientation domains and characteristics of Alzheimer’s disease (AD), as well as the striking neuroanatomical overlap between the orientation system and amyloid deposition and brain atrophy in AD, we hypothesized that disturbance of mental-orientation is a core-disorder in AD. In the presentation I will first present the ideas behind mental-orientation as well as its underlying brain system and its relation to the default mode network. I will present the current clinical understanding of Alzheimer’s disease and caveats it poses, and will supply behavioral and neuroimaging data supporting the central role of mental-orientation in the Alzheimer’s disease spectrum. I will conclude with reviewing current efforts in the unified research of space and time and its implication to Alzheimer’s disease.
Professor Ben Hur Tamir spoke to the Hebrew speaking group on the fascinating topic concerning ‘memory. As Director of the Brain Health and Neurology Department in Hadassah, his field is neurobiology. He told the audience that Dementia, and indeed Alzheimer’s is an illness that causes a loss of brain function due to sections of the brain being eaten away. In addition, depression or fear affect mental function. Once a patient is ready to admit to this, often memory improves. Alzheimer’s disease is not genetic, and it usually appears later in life. However one gene has been identified, and some genes carry risks. The illness can be triggered by other conditions such as blood pressure levels, Parkinsons, diabetes.
There are various tests that show whether a patient has the illness, as well as MRI scans, and there are medications that can remove antibodies, but by the time the antibodies are discovered it is too late to be effective.
Early detection of dementia or Alzheimer’s is the current key to thinking logically. Professor Ben Hur told us of research on a tribe in South America that showed that early hints of the disease show some 15 years before western testing can confirm its existence. The sooner the illness is found, symptoms can be attacked. Professor Shachar Arzi has developed a test that can be turned into an APP, and Professor Ruth Gabizon is working on oxidisation damage because weak anti-oxidants do not reach the brain.
He briefly suggested the use of Omega 3, Vitamin B and exercise to help protect against development of these illnesses.
SOURCE
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Alzheimer’s disease patients activate attention networks in a short-term memory task
Highlights
- • Patients with early AD succeeded in performing an fMRI short-term memory task.
- • Dorsal attention network activation did not differ between patients and controls.
- • Dorsal and ventral attention networks remained connected in high load task in AD.
- • DAN was necessary for the task, but not sufficient to reach normal performance.
Abstract
Network functioning during cognitive tasks is of major interest in Alzheimer’s disease (AD). Cognitive functioning in AD includes variable performance in short-term memory (STM). In most studies, the verbal STM functioning in AD patients has been interpreted within the phonological loop subsystem of Baddeley’s working memory model. An alternative account considers that domain-general attentional processes explain the involvement of frontoparietal networks in verbal STM beside the functioning of modality-specific subsystems. In this study, we assessed the functional integrity of the dorsal attention network (involved in task-related attention) and the ventral attention network (involved in stimulus-driven attention) by varying attentional control demands in a STM task. Thirty-five AD patients and twenty controls in the seventies performed an fMRI STM task. Variation in load (five versus two items) allowed the dorsal (DAN) and ventral attention networks (VAN) to be studied. ANOVA revealed that performance decreased with increased load in both groups. AD patients performed slightly worse than controls, but accuracy remained above 70% in all patients. Statistical analysis of fMRI brain images revealed DAN activation for high load in both groups. There was no between-group difference or common activation for low compared to high load conditions. Psychophysiological interaction showed a negative relationship between the DAN and the VAN for high versus low load conditions in patients. In conclusion, the DAN remained activated and connected to the VAN in mild AD patients who succeeded in performing an fMRI verbal STM task. DAN was necessary for the task, but not sufficient to reach normal performance. Slightly lower performance in early AD patients compared to controls might be related to maintained bottom-up attention to distractors, to decrease in executive functions, to impaired phonological processing or to reduced capacity in serial order processing.
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Re-evaluating the role of TPJ in attentional control: Contextual updating?☆
https://www.sciencedirect.com/science/article/pii/S0149763413002005#fig0010
Abstract
The right temporo-parietal junction (TPJ) is widely considered as part of a network that reorients attention to task-relevant, but currently unattended stimuli (Corbetta and Shulman, 2002). Despite the prevalence of this theory in cognitive neuroscience, there is little direct evidence for the principal hypothesis that TPJ sends an early reorientation signal that “circuit breaks” attentional processing in regions of the dorsal attentional network (e.g., the frontal eye fields) or is completely right lateralized during attentional processing. In this review, we examine both functional neuroimaging work on TPJ in the attentional literature as well as anatomical findings. We first critically evaluate the idea that TPJ reorients attention and is right lateralized; we then suggest that TPJ signals might rather reflect post-perceptual processes involved in contextual updating and adjustments of top-down expectations; and then finally discuss how these ideas relate to the electrophysiological (P300) literature, and to TPJ findings in other cognitive and social domains. We conclude that while much work is needed to define the computational functions of regions encapsulated as TPJ, there is now substantial evidence that it is not specialized for stimulus-driven attentional reorienting.
image description
Fig. 1. Peak voxel coordinates for attention, theory of mind, and empathy. Coordinates were derived from the meta-analysis by Decety and Lamm, 2007a, Decety and Lamm, 2007b. Additional data points from more recent studies have also been added to the visualization (see Table 1 for references of studies included). Images of the peak voxel coordinates in MNI space were created using GingerALE (www.brainmap.org) and are depicted on the MRIcroN (http://www.mccauslandcenter.sc.edu/mricro/mricron/) template brain.
Fig. 2. Illustration of the anatomical location of the parietal cortex from the Automatic Anatomical Labeling (AAL) atlas (Tzourio-Mazoyer et al., 2002) (A) and the cytoarchitectonic parietal maps of the Juelich atlas (Eickhoff et al., 2005) (B). The maps are depicted on the flattened brain surface of the PALS atlas as implemented in Caret 5.65 (Van Essen, 2005). SPL: superior parietal lobe, IPL: inferior parietal lobe, AG: angular gyrus, SMG: supramarginal gyrus, STG: superior temporal gyrus, MTG: middle temporal gyrus.
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The role of the right temporoparietal junction in attention and social interaction as revealed by ALE meta-analysis
Abstract
The right temporoparietal junction (rTPJ) is frequently associated with different capacities that to shift attention to unexpected stimuli (reorienting of attention) and to understand others’ (false) mental state [theory of mind (ToM), typically represented by false belief tasks]. Competing hypotheses either suggest the rTPJ representing a unitary region involved in separate cognitive functions or consisting of subregions subserving distinct processes. We conducted activation likelihood estimation (ALE) meta-analyses to test these hypotheses. A conjunction analysis across ALE meta-analyses delineating regions consistently recruited by reorienting of attention and false belief studies revealed the anterior rTPJ, suggesting an overarching role of this specific region. Moreover, the anatomical difference analysis unravelled the posterior rTPJ as higher converging in false belief compared with reorienting of attention tasks. This supports the concept of an exclusive role of the posterior rTPJ in the social domain. These results were complemented by meta-analytic connectivity mapping (MACM) and resting-state functional connectivity (RSFC) analysis to investigate whole-brain connectivity patterns in task-constrained and task-free brain states. This allowed for detailing the functional separation of the anterior and posterior rTPJ. The combination of MACM and RSFC mapping showed that the posterior rTPJ has connectivity patterns with typical ToM regions, whereas the anterior part of rTPJ co-activates with the attentional network. Taken together, our data suggest that rTPJ contains two functionally fractionated subregions: while posterior rTPJ seems exclusively involved in the social domain, anterior rTPJ is involved in both, attention and ToM, conceivably indicating an attentional shifting role of this region.
SOURCE
Published online 2014 Jun 11. doi: 10.1007/s00429-014-0803-z
Hadassah International Symposium in Neurology
Seventieth Anniversary of the Department of Neurology and in Honor of Oded Abramsky
Magid Auditorium
Hadassah Hebrew University Medical Center, Ein Kerem, Jerusalem
June 3-5, 2007
The Department of Neurology at Hadassah University Hospital, is pleased to celebrate the 70th anniversary of its founding. The celebration will take place in Jerusalem, June 3-5, 2007. The department was founded by the late Lipman Halpern who emigrated from Berlin to Jerusalem; He served as chairman until 1969, followed by Shaul Feldman who served until 1988 and Oded Abramsky who served until the end of 2005. The 70th anniversary is an historic event for Hadassah Medical Organization and the Hebrew University Hadassah Medical School. This occasion provides an opportunity to reflect on how the department came into being, to acknowledge the people who brought the department to this point, and the continuing role the department of neurology plays in patient care, research, education and community service. To honor seventy years of activities and achievements, the department is hosting an international forum of world-renowned neurologists. The event will honor the conclusion of Oded Abramsky’s term as chairman and the assumption of this role by Tamir Ben-Hur.
The scientific symposium includes overview presentations in various fields of clinical neurosciences by invited neurologists and Nobel Prize Laureates as well as presentations by members of the department of neurology.
We warmly welcome you to the symposium in Jerusalem.
Scientific Program
Sunday June 3, 2007
09:00 – 09:45 Opening Session
Chairpersons: Michael Sela (Weizmann Inst.)
Shaul Feldman (Hadassah)
Oded Abramsky (Hadassah)
Welcome: Tamir Ben-Hur Chairman, Department of Neurology, Hadassah
Greetings: Shlomo Mor-Yosef Director General, Hadassah Medical Organization
Menachem Magidor President, Hebrew University of Jerusalem
Ruth Arnon Vice President, Israel Academy of Sciences
Yoram Blachar Chairman, Israel Medical Association
Avinoam Reches Chairman, Israel Neurological Association
Johan Aarli President, World Federation of Neurology
09:45 – 11:15 Second Session
Neurodegeneration and protein degradation in disease
Chairpersons: Burton Zweiman (Univ. Pennsylvania)
Douglas L. Arnold (McGill Univ.)
Bella Gross (Technion, Nahariya Hosp.)
09:45 – 10:05 Stanley B. Prusiner Nobel Prize Laureate (UCSF)
Overview: Prion diseases
10:05 – 10:25 Aaron Ciechanover Nobel Prize Laureate (Technion, Haifa)
Ubiquitin-mediated protein degradation:
From basic mechanisms to the patient bed
10:25 – 10:45 Roger Rosenberg (Univ. Texas)
Neurodegenerative diseases: New strategies in research and therapy10:45 – 11:00 Scott A. Small (Columbia Univ.)
Alzheimer’s disease and aging
11:00 – 11:15 Howard L. Weiner (Harvard Univ.)
Immunological treatments in neurodegenerative diseases
11:15 – 11:40 Coffee Break
11:40 – 13:05 Third Session
Paraneoplastic and Infectious diseases
Chairpersons: Jack Antel (McGill Univ.)
Howard L. Lipton (Univ. Illinois Chicago)
Roni Milo (Ben-Gurion Univ., Barzilai Hosp.)
11:40 – 12:00 Jerome B. Posner (Memorial Sloan-Kettering)
Overview: Paraneoplastic syndromes
12:00 – 12:20 Richard T. Johnson (Johns Hopkins Univ.)
Overview: Neurovirology: State of the art
12:20 – 12:35 Donald H. Gilden (Univ. Colorado)
Antigen identification in MS
12:35 – 12:50 Peter G.E. Kennedy (Glasgow Univ.)
Neuropathogenesis of human trypanosomiasis (sleeping sickness)
12:50 – 13:05 Francisco Gonzalez-Scarano (Univ. Pennsylvania)
NeuroAIDS
13:05 – 13:55 Lunch Break
13:55 – 15:25 Fourth Session
Epilepsy, vascular and extrapyramidal disorders
Chairpersons: Robert B. Daroff (Case Western Reserve Univ.)
Stephen Davis (Melbourne Univ.)
Rivka Inzelberg (Tel Aviv Univ., Meir Hosp.)
13:55 – 14:15 Frederick Andermann (McGill Univ.)
Overview: Epilepsy: State of the art
14:15 – 14:30 Timothy A. Pedley (Columbia Univ.)
Understanding epileptogenesis: A beginning
14:30 – 14:50 Louis R. Caplan (Harvard Univ.)
Overview: Cerebrovascular diseases: State of the art
14:50 – 15:05 Vladimir Hachinsky (London Univ., Ontario)
Vascular dementia
15:05 – 15:30Stanley Fahn (Columbia Univ.)
Overview: Parkinson’s disease and other extrapyramidal disorders
15:30 – 15:55 Coffee Break
15:55 – 17:15 Fifth Session
Neuromuscular disorders
Chairpersons: Klaus V. Toyka (Univ. Wurzburg)
Aksel Siva (Istanbul Univ.)
David Yarnitsky (Technion, Rambam Hosp.)
15:55 – 16:20 George Karpati (McGill Univ.)
Overview: Muscle diseases: State of the art
16:20 – 16:40 John Newsom-Davis (Oxford Univ.)
Neuromuscular junction disorders
16:40 – 17:00 Gerard Said (Bicetre Univ.)
Overview: Peripheral neuropathy: State of the art
17:00 – 17:15 Robert P. Lisak (Wayne State Univ.)
Schwannopathies
Monday June 4, 2007
09:00 – 10:10 Sixth Session
Sandy and Peter Collins Lectures on MS
Chairpersons: Ioannis Milonas (Aristotle Univ.)
Tomas Olsson (Karolinska Inst.)
Ariel Miller (Technion, Carmel Hosp.)
09:00 – 09:20 Reinhard Hohlfeld (Munich Univ.)
Immunology of multiple sclerosis
09:20 – 09:40 Hans Lassmann (Univ. Vienna)
Pathology of multiple sclerosis
09:40 – 09:55 Hans-Peter Hartung (Heinrich-Heine Univ.)
Current therapies in multiple sclerosis
09:55 – 10:10 Lawrence Steinman (Stanford Univ.)
Future therapies in multiple sclerosis
10:10 – 10:30 Coffee Break
10:30 – 11:40 Seventh Session
Stem cells and Neurology
Chairpersons: Leslie P. Weiner ( Univ. South Carolina)
Krzysztof Selmaj (Lodz Univ.)
Joab Chapman (Tel Aviv Univ., Sheba Hosp.)
10:30 – 10:50 Evan Y. Snyder (Burnham Inst., La Jolla)
Overview: stem cells therapy
10:50 – 11:10 Ian D. Duncan (Univ. Wisconsin)
Remyelination in the CNS
11:10 – 11:25 Douglas Kerr (Johns Hopkins Univ.)
Cell therapy for neurogenerative diseases
11:25 – 11:40 Jeff W.M. Bulte (Johns Hopkins Univ.)
Molecular neuroimaging of cell therapy
11:40 – 12:50 Eight Session
Agnes Ginges Lectures in Neurogenetics
Chairpersons: Steve P. Ringel (Univ. Colorado)
Anna Czlonkowska (Inst. Psychiatry-Neurology, Warsaw)
Boaz Weller (Technion, Bnai Zion Hosp.)
11:40 – 12:00 Stefano Di Donato (Carlo Besta Inst., Milano)
Overview: Neurogenetics: State of the art
12:00 – 12:20 Salvatore DiMauro (Columbia Univ.)
Mitochondrial diseases
12:20 – 12:35 Stefan M. Pulst (UCLA)
Ion channels dysfunction in genetic spinocerebellar syndromes
12:35 – 12:50 Alastair D.S. Compston (Cambridge Univ.)
Genetics of MS and other demyelinating disorders
12:50 – 13:40 Lunch Break
13:40 – 16:35 Ninth Session
Department of Neurology, Hadassah: Research highlights
Chairpersons: Yair Birnbaum (Director, Hadassah Univ. Hosp., Ein Kerem)
Milton Alter (Temple Univ.)
Itzhak Wirguin (Ben-Gurion Univ.)
13:40 – 13: 55 Tamir Ben-Hur
Stem cell therapy in neurological diseases
13:55 – 14:10 Dimitrios Karussis
Neuroprotection in MS
14:10 – 14:25 Talma Brenner
Pregnancy, alphafetoprotein, EAE and MS
14:25 – 14:40 Ruth Gabizon
When prions meet other pathological insults
14:40 – 14:55 Hanna Rosenmann
Novel animal models of Alzheimer’s disease and tauopathy
14:55 – 15:05 Tali Siegal
Longitudinal assessment of genetic and epigenetic markers in progressive oligodendroglial tumors
15:05 – 15:15 Ronen R. Leker
Manipulation of endogenous neural stem cells in stroke
15:15 – 15:25 Netta Levin
Plasticity in the human visual cortex: fMRI studies
15:25 – 15:35 Dana Ekstein
The role of zinc in epileptogenesis
15:35 – 15:45 Shahar Arzi
Remembering the future, predicting the past:
An electrophysiological study of mental time travel
15:45 – 16:05 Coffee break
16:05 – 16:20 Zohar Argov
One gene is not enough: Lessons from hereditary neuromuscular disorders identified at Hadassah
16:20 – 16:35 Alex Lossos
Adult genetic neurometabolic diseases: Hadassah’s experience
16:35 – 17:45Closing Session
Vision of future Neurology
Chairpersons: Ehud Razin (Dean, Hebrew University Hadassah Medical School)
Shlomo Rotshenker (Chairman, Israel Neuroscience Society)
Eldad Melamed (Tel Aviv Univ., Beilinson Hosp.)
Greetings: Ehud Olmert Israel Prime Minister
Avi Israeli Director General, Israel Ministry of Health
16:50 – 17:05 Natan M. Bornstein(Tel Aviv Univ., Ichilov Hosp.)
Neurology in Israel
17:05 – 17:25 Donald H. Silberberg (Univ. Pennsylvania)
Neurology in developing countries
17:25 – 17:45 Lewis P. Rowland (Columbia Univ.)
Prospects for neurology in the 21st century
Tuesday June 5, 2007
Seventieth Meeting of the HebrewUniversity Board of Governors
13:30
Dedication of :
“The Stanley B. PrusinerMedicalInformationCenter“
Hebrew University Hadassah Medical School
Judah Magnes Square, Ein Kerem, Jerusalem
REFERENCE for the Genetics of Alzheimer’s Disease
- Goate, A. et al. Segregation of a missense mutation in the amyloid precursor protein gene with familial Alzheimer’s disease. Nature 349, 704–706 (1991).
- Sherrington, R. et al. Cloning of a gene bearing missense mutations in early-onset familial Alzheimer’s disease. Nature 375, 754–760 (1995).
- Rogaev, E. I. et al. Familial Alzheimer’s disease in kindreds with missense mutations in a gene on chromosome 1 related to the Alzheimer’s disease type 3 gene. Nature 376, 775–778 (1995).
- Hardy, J. & Selkoe, D. J. The amyloid hypothesis of Alzheimer’s disease: progress and problems on the road to therapeutics. Science 297, 353–356 (2002).
- Ricciarelli, R. & Fedele, E. The amyloid cascade hypothesis in Alzheimer’s disease: it’s time to change our mind. Curr. Neuropharmacol. 15, 926–935 (2017).
- Doody, R. S., Farlow, M. & Aisen, P. S., Alzheimer’s Disease Cooperative Study Data Analysis and Publication Committee. Phase 3 trials of solanezumab and bapineuzumab for Alzheimer’s disease. N. Engl. J. Med. 370, 1460 (2014).
- Honig, L. S. et al. Trial of solanezumab for mild dementia due to Alzheimer’s disease. N. Engl. J. Med. 378, 321–330 (2018).
- Galimberti, D. & Scarpini, E. Disease-modifying treatments for Alzheimer’s disease. Ther. Adv. Neurol. Disord. 4, 203–216 (2011).
- Yiannopoulou, K. G. & Papageorgiou, S. G. Current and future treatments for Alzheimer’s disease. Ther. Adv. Neurol. Disord. 6, 19–33 (2013).
- Jagust, W. Imaging the evolution and pathophysiology of Alzheimer disease. Nat. Rev. Neurosci. 19, 687–700 (2018).
- Rajan, K. B., Wilson, R. S., Weuve, J., Barnes, L. L. & Evans, D. A. Cognitive impairment 18 years before clinical diagnosis of Alzheimer disease dementia. Neurology 85, 898–904 (2015).
- Rosenblum, W. I. Why Alzheimer trials fail: removing soluble oligomeric beta amyloid is essential, inconsistent, and difficult. Neurobiol. Aging 35, 969–974 (2014).
- Gatz, M. et al. Role of genes and environments for explaining Alzheimer disease. Arch. Gen. Psychiatry 63, 168–174 (2006).
- Wingo, T. S., Lah, J. J., Levey, A. I. & Cutler, D. J. Autosomal recessive causes likely in early-onset Alzheimer disease. Arch. Neurol. 69, 59–64 (2012).
- Saunders, A. M. et al. Apolipoprotein E epsilon 4 allele distributions in late-onset Alzheimer’s disease and in other amyloid-forming diseases. Lancet 342, 710–711 (1993).
- Strittmatter, W. J. et al. Apolipoprotein E: high-avidity binding to beta-amyloid and increased frequency of type 4 allele in late-onset familial Alzheimer disease. Proc. Natl Acad. Sci. USA 90, 1977–1981 (1993).
- Corder, E. H. et al. Protective effect of apolipoprotein E type 2 allele for late onset Alzheimer disease. Nat. Genet. 7, 180–184 (1994).
- Liao, F., Yoon, H. & Kim, J. Apolipoprotein E metabolism and functions in brain and its role in Alzheimer’s disease. Curr. Opin. Lipidol. 28, 60–67 (2017).
- Deane, R. et al. ApoE isoform-specific disruption of amyloid beta peptide clearance from mouse brain. J. Clin. Invest. 118, 4002–4013 (2008).
- Verghese, P. B., Castellano, J. M. & Holtzman, D. M. Apolipoprotein E in Alzheimer’s disease and other neurological disorders. Lancet Neurol. 10, 241–252 (2011).
- Harold, D. et al. Genome-wide association study identifies variants at CLU and PICALM associated with Alzheimer’s disease. Nat. Genet. 41, 1088–1093 (2009).
- Lambert, J. C. et al. Genome-wide association study identifies variants at CLU and CR1 associated with Alzheimer’s disease. Nat. Genet. 41, 1094–1099 (2009).
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