Transcript Convert - Coe College

Amnesia
Syndromes
Lesson 23
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
Protease regulating
region
amyloid
Beta region
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 ~
