neurobiology of dementia
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Neurobiology of Dementia. Majid Barekatain , M.D., Associate Professor of Psychiatry Neuropsychiatrist Isfahan University of Medical Sciences 27-28 Ordibehesht 1392 April 16-17, 2013. Dementing Illnesses: Proteinopathies. DAT: beta amyloid => posterior cortex (parietal / temporal) - PowerPoint PPT PresentationTRANSCRIPT
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Neurobiology of Dementia
Majid Barekatain, M.D.,Associate Professor of Psychiatry
NeuropsychiatristIsfahan University of Medical Sciences
27-28 Ordibehesht 1392April 16-17, 2013
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Dementing Illnesses: Proteinopathies
DAT: beta amyloid => posterior cortex (parietal / temporal)
FTD: tau => anterior cortex (frontal / temporal)
DLB: alpha synuclein => limbic system / midbrain / brain stem / cortex
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Neuritic Plaques
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Neurofibrillary Tangles
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Evidence for Beta Amyloid as the Putative Toxic Agent in DAT
• The clinical phenotype of AD corresponds to impairment in brain regions with the highest plaque burdens
• The degree of intellectual impairment in AD directly correlates with AB plaque burden
• Beta amyloid deposition is associated with inflammatory
changes in the cerebral cortex including cell death
• Most cases of familial AD are caused by mutations in genes regulating expression of presenilin
• DAT occurs uniformly in patients with Down’s syndrome (trisomy 21) at an early age
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DAT: Distribution of Neuritic Plaques
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DAT: Distribution of NFT
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Dement Geriatric Cogn Disord 2001; 12: 198-205
Coronal Image of the Brain of an Older Adult with Normal Cognition
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Dement Geriatric Cogn Disord 2001; 12: 198-205
Brain MRI Images of Older adults with a) Alzheimer’s Disease b) Normal Cognition and c) DLB
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Flurodeoxyglucose (FDG) PET
normal DAT
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Metabolism of the Amyloid Precursor Protein
Beta Secretase Cleavage Site
Alpha Secretase Cleavage Site 17
Gamma Secretase Cleavage Site 40-42
A Beta domain
Amyloid Precursor Protein
1
40-42
1
770
17
Cell
mem
bran
e
Gamma Secretase
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Proteolytic Cleavages of APP to Produce A Peptide
Selkoe DJ et al. JAMA. 2000;283:1615-1617.
-amyloid precursor protein
-secretase
A peptide
-secretase
Extracellular space
TM Cytoplasm
COOHNH2
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Proteolysis of the APP
1. APP + alpha secretase + gamma secretase = P3 (soluble) 17
40-42
2. APP + beta secretase + gamma secretase = AB (insoluble) 1
40-42
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Dementia of Lewy Body• Dementia with Lewy bodies overlaps clinically with Alzheimer’s
disease and Parkinson’s Disease.• DLB often has a rapid or acute onset, with especially rapid decline
in the first few months. DLB tends to progress more quickly than Alzheimer’s disease.
• fluctuating cognition with great variations in attention and alertness from day to day and hour to hour, recurrent visual hallucinations (observed in 75% of people with DLB), and motor features of Parkinson's.
• Suggestive symptoms are REM-sleep behavior disorder.• hypersensitivity to neuroleptic and antiemetic medications
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DLB
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Differential Diagnosis
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Vascular Dementia
• Dementia caused by problems in supply of blood to the brain, typically by a series of minor stroke.
• Was previously referred to as "multi-infarct dementia”
• Vascular dementia is the second most common form of dementia after Alzheimer’s Disease (AD) in older adults.
• Presents with cognitive impairment, acutely or subacutely, after an acute cerebrovascular event.
• After the onset a stepwise progression is typical.
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Vascular Dementia
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•Who can suggest the next case!?
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Dementia Due to Head Trauma
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