alzheimer's and amnesias

inheritance

autosomal dominant

• presenilin 1 and 2 gene → processing amyloid precursor protein

• trisomi 21

what 2 proteins causes alzheimer’s

B amyloid and tau tangles

what degenerates

limbic system:

basal nucleus of meynerts → entorhinal cortex → hippocampus → other limbic cortices → neocortex

how are B amyloids pathogenic

1. Amyloid precursor proteins are usually processed by a secretase → non amylidogenic

2. Beta and Gamma secretase → amyloidogenic fragments → protofibrils which are neurotoxic

3. protofibrils aggregate in high [Ca2+] → Beta amyloid plaque

4. plaque deposits in vessel walls

how

are tau tangles pathogenic

1. coded by MAPT gene

2. involved in axon transport b via the formation of microtubules

3. tubules shorted by desphophorylation and elongated by phosphorylation

4. hyperphosphorylation causes protein aggregation → paired helical filament called neuropil thread

5. neuropil threads are long and inflexible → tangle to form neurofibrillary tangles → cells death

how do tau and B amyloid cause damage

activate microglia via CD68 → gliosis

how does Apolipoprotein E affect alzheimers

1. APOE4: increases age of onset and severity

2. APOE3: no effects

3. APOE2: protective against alzheimer’s

symptoms:

retrograde amnesia:

1. loss of episodic memory + working memory + some semantic memory

2. end stage loss of procedural memory

what causes demetia

alpha synuclein lewy bodies

1. no impact on movement

what is vascular dementia

narrowing of blood vessels → mini strokes → decreased O2 → progressive cognitive decline

wernicke-korsakoff syndrome

chronic alcohol causes thiamine deficiency (B1)

1. wernicke’s encephalopathy: damage to the vermis causes ataxia, nystagmus, confusion, vertigo

2. korsakoff syndrome: damage to mammilary bodies and anterior thalamus causes → profound anterograde amnesia with some retrograde amnesia