Gero 310 F'09 neuro 4

Gero 310 F'09 neuro 4 - Alzheimers disease Basic...

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Alzheimer’s disease • estimated 4.5 million Americans have the disease - many, many more in early stages of disease • based upon 2000 US census data, by 2050 estimate 13 million Americans will be afflicted • treatments: no cures, a few medications that provide symptomatic benefits; one newer medication that may slow progression • if a treatment would delay onset by 5 years, it would reduce by 50% the number of AD patients in the next 50 years Basic information and statistics compiled by Alzheimer’s Association
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AD is one of several age-related dementias • dementia is a broad diagnostic category - refers to memory impairment plus at least one other significant cognitive deficit: - impaired comprehension - reduced speech abilities - loss of executive function (making decisions) - change in mood, personality - impaired activities of daily living (ADL) - dressing, eating, toileting, etc. • many disorders are associated with dementia component, including PD, alcoholism, depression, multi-infarct dementia
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Alzheimer’s disease - accounts for 50+% of all dementia - heterogeneous disorder; several subtypes - both genetic and sporadic forms - heritable = familal AD - unknown cause = sporadic AD - AD is fatal; typical course 8-10 years although variable - neurodegeneration eventually affects vital regions in brainstem and is widespread - risk factors: - age: incidence doubles every 5 years (~50% over 80) - head injury - gender: female - family history ( genetic risk factors ) • AD is a neurodegenerative disorder, it causes brain atrophy AD neuropathology
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‘plaques’ β -amyloid deposits ‘tangles’ insoluble filaments of tau dystrophic neurites
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Neurofibrillary tangles (NFTs) - a marker of dead and dying neurons - not all dead neurons in AD brain form NFTs aged AD * neurofibrillary tangles abundant in AD brain but sparse in aged - absent in young adults - not specific to AD; found in other disorders
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AD involves progressive but selective neuronal damage and death - not all brain regions affected - initial damage found in areas that affect learning & memory - entorhinal cortex, hippocampus one lesion is called NFT or neurofibrillary tangle - NFTs form first in live cells - remain as marker of dead - not all dead cells have NFT - hyperphosphorylation of tau (microtubules)
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Plaques: accumulations of β -amyloid protein - β -amyloid is perhaps the key molecule in the pathogenesis of AD • plaques (aka senile plaques) - largely comprised of a previously unknown protein called β -amyloid - small protein (40-42 amino acids, ~4 kDa) - normal protein, present in biological fluids in a soluble state at low levels - in AD, -amyloid self-associates; forms aggregates - highly insoluble - deposits extracellularly in the form of plaques
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β -Amyloid P laques SIGMA-ALDRICH
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β -amyloid aggregates • abnormal • insoluble β -amyloid protein • normal • soluble β -amyloid protein spontaneously forms aggregates β -amyloid oligomers • normal? • soluble
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This note was uploaded on 01/16/2011 for the course GERO 310 taught by Professor Davies during the Fall '09 term at USC.

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Gero 310 F'09 neuro 4 - Alzheimers disease Basic...

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