L08.AD - Alzheimer's Disease Edward Koo, M.D. Department of...

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Alzheimer's Disease Edward Koo, M.D. Department of Neurosciences Shiley-Marcos Alzheimer's Disease Research Center University of California, San Diego BIPN 150 Diseases of the Nervous Systen January 29, 2009
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Incidence of Alzheimer's disease 55 65 75 85 95 0 2 4 6 8 10 New Cases/100/year AD Incidence Rates E. Boston Rochester Hisayama Lundby Framingham Rochester ± In 2000, U.S. Population was 280 million ± 12.5% over age of 65 (35 million) ± 15% over age 65 have dementia (5.3 million) ± Two-thirds due to Alzheimer's disease (3.5 million)
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± Progressive, irreversible brain disorder ± Gradually destroys memory and ability to learn, reason, communicate, make judgments, and carry out daily activities ± Fatal (death usually occurs within 8²10 years of diagnosis) ± 4th leading cause of death for Americans over 65 ± 37 million affected worldwide What is Alzheimer·s Disease?
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Symptomatology and progression of AD AD progression Mild ± MMSE >20 ² Forgetfulness ² Problems with shopping, etc. ² Depression Mod ± MMSE 10-20 Severe ± MMSE<10 Ƃ Impairment of recent memory Ƃ Require help with ADLs Ƃ Delusions Ƃ Limited language Ƃ Loss of basic ADLs Ƃ Agitation, incontinence
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What are neurodegenerative diseases? ± Progressive loss of neurons with associated astrogliosis and secondary white matter changes ± Selective loss of neurons (by region, transmitter systems, etc.) ± No inciting events that predispose to these changes ± Rare genetic mutations produce virtually identical diseases ± Occasional pathological hallmarks, etc. ± Lewy bodies in Parkinson's disease ± Examples: ± Alzheimer's disease, Huntington disease and other polyglutamine disorders, Creutzfeldt-Jakob disease (aka ´prion diseasesµ, ´mad cowµ), Parkinson's (loss of dopaminergic neurons), multi-system atrophies
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Idiopathic Parkinson's disease
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Ƃ What causes it in most cases Ƃ How to definitively diagnose it in live patients Ƃ How to prevent it Ƃ How to treat it Ƃ 4 medicines approved for amelioration of symptoms Ƃ 0 medicines currently available to treat underlying disease There·s a lot we don·t know about AD
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Alzheimer's Pathology ± Senile (amyloid) plaques ± Neurofibrillary tangles ± Neuronal loss ± Synapse loss ± Inflammatory responses
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Alzheimer·s Disease Pathology Amyloid Plaques and Neurofibrillary Tangles Neuronal Degeneration and Loss of Synapses Impaired Neuronal Activity Normal Alzheimer¶s Disease Normal Alzheimer¶s Disease Brain Atrophy
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Why are synapses lost and why do neurons die in AD? AD control control AD
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Alzheimer's pathology
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A b is released after two cleavages and deposited in senile plaques in brain
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1970s: Description of cholinergic deficiency and cholinergic hypothesis 1984: Purification of ǀ-amyloid from plaques (Glenner, UCSD) 1985: Demonstration of tau protein in tangles
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This note was uploaded on 04/01/2009 for the course BIPN 150 taught by Professor Fortes during the Winter '09 term at UCSD.

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L08.AD - Alzheimer's Disease Edward Koo, M.D. Department of...

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