Amnesia Syndromes

Lesson 22

Wernicke-Korsakoff’s Syndrome

Deficits similar to H.M. Anterograde retrograde more severe

Cause: Long-term alcohol abuse Thiamine (vitamin B1 ) deficiency required for glucose utilization Neurons die ~

Damage to Diencephalon

Hypothalamus Mammilary bodies mammilothalamic tract

Thalamus reciprocal inputs w/ prefrontal cortex temporal sequence ~

Alzheimer’s Disease

Profound memory loss 1/4 of all 85-yr-olds

Effects on memory Procedural O.K. Declarative deficits Personality changes

Diagnosis only certain at autopsy Widespread brain atrophy plaques and tangles ~

Neurofibril Tangles

Inside neuron Forebrain & cortex

Tau proteins toxic abnormal ~

Amyloid Plaques Extracellular Beta amyloid protein

From degenerating neurons

Found in everyone More abundant in

Alzheimer’s patients ~

Alternate Enzymatic Splicing?

Beta amyloid precursor protein BAPP

Cleaved by enzyme normal protein beta amyloid ~

Alternate splicing model: BAPP

amyloidBeta region

Protease regulatingregion

Alternate splicing model: BAPP

Normal splicing

Alternate splicing model: BAPP

Alternative splicing

Alternate splicing model: BAPP

Alternative splicing

Beta amyloid

Causes: Genetic Model

Very old mild nonfamilial form Chromosome 21 trisomy BAPP gene encoding amyloid Apolipoprotein E - APOE Gene variant & onset age

correlated Down’s Syndrome also trisomy

Adults Alzheimer’s ~

Cholinergic Degeneration

Decreased Cholinergic activity Postsynaptic

receptors populations OK

Ach-releasing neurons die off ~

Treatment?

Choline? not effective

ACh agonists? AChE inhibitors Tacrine effective in 33%

Stem cells?

Chronic Inflammation Model Anti-inflammatory (NSAID) slowed progression Arthritic patients treated with NSAIDs less likely to have Alzheimer’s Microglia Phagocytosis Overactive inflammatory response? ~

Recent Developments

Role of beta amyloid & Tau cause or effect?

Abnormal beta amyloid is causal successfully blocked triggers changes in Tau

Tau neurofibrillary tangles are toxic

Beta amyloid detected in CSF ~