Alzheimers

Question 1

Gross changes

Answer 1

• diffuse atrophy
• flattened cortical sulci
• enlarged cerebral ventricles

Question 2

Histological changes

Answer 2

• neuronal loss
• synaptic loss
• granulovascular degeneration (small vacuoles with central granules in the cytoplasm of neurons, especially in the temporal lobes)
• senile plaques
• neurofibrillary tangles
• Hirano bodies
• astrocytic fliosis and micoglial activation are also noted in some cases

Question 3

Senile plaques

Answer 3

• insoluble amyloid peptide deposits
• peptide involved is AB (beta A4) peptide
• amyloids are fibrils of multmeric chanins of pepotides deposited extracellularly
• they have a beta pleated sheet formation
• AB is cleave from amuloid-B-precursor protein by B- and gamma secretases
• 2 main subtypes: neurticic plaques and diffuse plaques

Question 4

Neuritic plaques

Answer 4

• contain AB in form of amyloid fibrils, among which are irregularly swollen dystrophic neurites
• neurites are seen with silver stains
• contain dense central core of amyloid
• seen in Downs and in normal ageing
• ‘apple green birefringence’ is seen with congo red staining

Question 5

Diffuse plaques

Answer 5

• consist of largely non-fibrillar extracellular AB
• not related to degree of cognitive decline
• only neuritic plaques are counted in neuropathological tests

Question 6

Neurofibrillary tangles

Answer 6

• consist of abnormally phosphorylated tau protein
• one of several degenerative tauopathies
• tau is needed for microtubule assembly
• apart from AS, NFTs occur in Downs, dementia pugilistica, Parkinson-dementia complex of Guam, Hallervorden-Spatz disease and the normal elderly
• most tangles are basophilic
• tangles are mostly intraneuronal but on neuronal degeneration they may appear extracellularly
• Braak and Braak stages v-vi indicated AD

Question 7

Hirano bodies

Answer 7

• rod shaped eosinophilic bodies in the cytoplasm of neurons
• seen in extracellular space when the neuron dies
• intracellular aggregates of actin and actin associated proteins
• frequently seen in hippocampal pyramidal cells

Question 8

Cerebral Amyloid Angiopathy

Answer 8

• CAA is the accumulation of AB in the walls of blood vessels in the cerebral cortex and leptomininges
• affects about 30% of normal elderly people but over 90% with AD
• important cause of strokes in the elderly

Question 9

Binswanger disease

Answer 9

• subcortical vascular dementia
• or subcortical arteriosclerotic encephalopathy
• characterised by the presence of many small infarctions of the white matter that spares the cortical regions
• often coexists with AD-type changes

Question 10

Hippocampal pathology

Answer 10

• specific pattern of neuronal loss seen in subiculum of the hippocampal formation and layers II and IV of the entorhinal cortex
• the affected cells connect huppoampal formation with the assocation cortices, basal forebrain, thalamus and hypothalamus, structures crucial to memory
• pattern of neuronal loss isolates the hippocampal formation from its input and output contributing to the memory disorder of AD patients

Question 11

Correlation to cognitive decline

Answer 11

• number and distribution of tangles increases as cognitive decline increases
• when both neuritic plaques and tangles are presentm the presence of even a few tangles in a single field in the neocortex suggests a significant cognitive decline
• neuritic plaques are less important#
• tangles more important
• best neuropathological correlate of decline is actually the number of synapses
• the marker for synapses is the antibody to synaptophysin,a protein found in the presynaptic endings