25 th Annual Southern California Alzheimer s Disease Research Conference
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1 25 th Annual Southern California Alzheimer s Disease Research Conference New Guidelines and Importance of Brain Donation Thomas J. Montine, MD, PhD Alvord Professor & Chair Department of Pathology University of Washington
2 National Alzheimer s Project Act (NAPA) Signed into law by President Obama January 2011 National Plan to Address Alzheimer s Disease Preventing and effectively treating Alzheimer s disease, including Alzheimer s disease related dementias, by 2025
3 Scientific and Medical Input to NAPA Alzheimer's Disease Research Summit 2012: Path to Treatment and Prevention Alzheimer s Disease Related Dementias: Research Challenges and Opportunities Neurology, 2014
4
5 Cognitive Impairment and Dementia Syndrome In older adults An idiosyncratic convergent trait AD, VBI, LBD, HS Caused by chronic diseases Dementia Prodrome Latency In middle-aged adults Less co-morbidity AD, FTD, LBD
6 Molecular Complexity 22 IGAP loci CLU SORL1 ZCWPW1 APOE, ABCA7, BIN1, CASS4, MEF2C, PICALM CR1 MS4A6A CD33 GWAS: Cases & Controls VBI none CAA - APOE LBD - APOE HS - KCNMB Future Molecular phenotype Brain CSF
7 AD Research Summit 2012 (NIA) AD dementia G. McKhann Alzheimer's & Dementia 2011;7: Mild Cognitive Impairment due to AD M. Albert Alzheimer's & Dementia 2011;7: Toward defining preclinical stages of AD R. Sperling Alzheimer's & Dementia 2011;7: Guidelines for neuropath assessment of AD B. Hyman and T. Montine Alzheimer's & Dementia 2012;8: citations Acta Neuropathol. 2012;123: citations
8 AD-Related Dementias 2013 (NINDS & NIA) Fronto-temporal dementia Lewy Body Disease Vascular Brain Injury Multi-etiology dementia Health Disparities T. Montine Neurology, August 2014
9 Parkinson s Disease 2014 (NINDS) Motor and non-motor symptoms (including dementia) T. Montine Annals of Neurology, September 2014
10 2012 Guidelines for neuropath assessment Thomas G. Beach Eileen H. Bigio Nigel J. Cairns Dennis W. Dickson Charles Duyckaerts Matthew P. Frosch Bradley T. Hyman Eliezer Masliah Suzanne S. Mirra Thomas J. Montine Peter T. Nelson Creighton H. Phelps Julie A. Schneider Dietmar Rudolf Thal John Q. Trojanowski Harry V. Vinters
11 Major Changes to NP Assessment Issue Dx of dementia required for NP AD NP assessment Common co-morbid diseases Yes Braak stage and CERAD score Little guidance No These plus Thal phase Explicit Minimum regions Silent Explicit Reporting and CPC Silent Guidelines
12 AD Neuropathologic Change
13 A (amyloid) Score Cerebral cortex Neostriatum Cerebellum
14 B (Braak) Score in primary visual cortex PHF-1 antibody was generously provided by Dr. Peter Davies
15 Lewy Body Disease
16 Lewy Body Disease DMN X Substantia Nigra Amygdala Anterior Cingulate Superior Temporal G Anti-alpha-synuclein antibody KM51 (Novocastra, Newcastle, United Kingdom)
17 CVD Cerebrovascular Disease and Vascular Brain Injury Report using standardized approach VBI Record size and location of gross infarcts Enumerate microinfarcts in standard screening sections > 2 sufficient to explain cognitive impairment
18
19 CVD Cerebrovascular Disease and Vascular Brain Injury Report using standardized approach VBI Record size and location of gross infarcts Enumerate microinfarcts in standard screening sections > 2 sufficient to explain cognitive impairment
20
21 Major Challenges Remain Almost all of our knowledge about dementia in the US comes from people of European decent Incomplete knowledge about disease mechanisms Knowledge about potential interactions is very limited AD VBI meeting held by NINDS and AA in 2014 Representative experimental models are needed to fuel therapeutic discovery
22 Fall 2014 Updated milestones 9-11 February 2015 AD Research Summit II Winter 2016 ADRD II 2025 Next Steps Preventing and effectively treating Alzheimer s disease, including Alzheimer s disease related dementias, NAPA
23 Thank you
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