Neuropathology Flashcards
Histological changes in Alzheimer’s?
Neuronal loss in cortex and hippocampus Synaptic loss Granulovascular degeneration Senile plaques Neurofibrillary tangles Hirano bodies
What is granulovascular degeneration?
Small vacuoles with central granules in cytoplasm of neurons - particularly in temporal lobes
What cleaves beta A4?
Cleaved from amyloid-beta precursor protein by beta and gamma-secretases
How are neuritic plaques visualized?
Neurites visualized with silver stains.
May be seen as an eosinophilic mass on haematoxylin and eosin stains.
Diseases in which neuritic plaques are seen?
Normal ageing
Downs
What are neurofibrillary tangles composed of?
Cytoskeletal elements - primarily abnormally phosphorylated tau protein.
What stimulates formation of abnormal tau?
Beta A4 peptide interacts with cholinergic receptors, stimulating abnormal hyperphosphorylation of tau.
How can hyperphosphorylated tau be visualised?
Staining with antibody to abnormal tau
Which conditions do neurofibrillary tangles occur in?
Alzheimers Downs Dementia pugilistica (punch-drunk syndrome) Parinkson-dementia complex of Guam Hallervorden-Spatz disease Normal elderly
Structure of Hirano bodies?
Rod-shaped eosinophilic bodies n cytoplasm of neurons
Intracellular aggregates of actin and actin-associated proteins
Pathology of cerebral amyloid angiopathy?
Accumulation of A beta in walls of blood vessels, particularly arteries and arterioles in cerebral cortex overlying leptomeninges
What % of the elderly have Cerebral amyloid angiopathy?
30%
What % of patients with Alzheimer’s have Cerebral Amyloid Angiopathy?
90%
Relation between tangles and cognitive decline
Increase in number and distribution
Best neuropathological correlate of decline?
Number of synapses
Marker for synapses?
Antibody to synaptophysin, a protein found in presynaptic endings
What is Binswanger’s Disease?
Subcortical vascular dementia/subcortical arteriosclerotic encephalopathy
Many small infarctions of what matter that spares cortical regions.
Co-exists with Alzheimer’s-type changes
Histology of Lewy bodies?
Weakly eosinphilic
Spherical
Cytoplasmic inclusions
Correlation between number of Lewy bodies and cognitive decline?
None
What can we use to identify Lewy body?
Antibody to protease ubiquitin
Staining with alpha-synuclein antibodies
What do lewy bodies contain?
Accumulations of alpha-synuclein
What does alpha-synuclein do?
Accelerates reuptake of dopamine in neurons; this dopamine overload may be toxic
Where does microvacuolation occur in Lewy Body Dementia?
Microvacuolation of cerebral cortex, mainly in medial temporal region.
Name some tauopathies?
Alzheimers
Picks
Progressive supranuclear palsy
Corticobasal degenerations
Name some synucleopathies?
Parkinsons
Lewy Body Dementia
Multisystem atrophy
Most common type of frontotemporal dementia?
Frontal lobe degeneration
Characteristics of Picks disease?
Prepronderance of atrophy in frontotemporal regions
What are Pick cells?
Abnormal swollen oval-shaped neuronal cells with loss of Nissl’s substance and peripherally displaced nucleus
Most common form of CJD?
Sporadic
What is variant CJD related to?
Bovine spongiform encephalopathy
Which gene encodes prion protein?
On chromosome 20
What does PrPSc do?
Protease-resistant
Accumulates in CNS
Triggers conversion of normal PrPc to PrPSc
How can PrPSc be identified?
Immunoperoxidase staining
Pathology in vCJD?
Marked accumulation of prion protein
Plaques are florid
What protein is found in CSF in CJD
14-3-3
In which type of CJD are the EEG changes lacking?
Familial
In which type of CJD are 14-3-3 proteins absent?
Familial - <50%
Which phenotype of codon 129 at PrP is present in CJD?
M/M phenotype
What % of people with sporadic CJD have M/M phenotype?
73%
What % of people with variant CJD have M/M phenotype?
100%
Most supportive diagnostic test for CJD?
MRI
Which type of MRI most shows pulvinar sign?
FLAIR sequences of MRI
EEG signs in classic CJD?
Triphasic, sharp waves
Major HIV receptors?
CD4
CD8
Source of CNS infection in HIV?
Infected CD4+ T cells and monocytes
Most commonly infected neurocells of HIV-1?
Perivascular macrophage and microglia
Which factors cause demyelination of oligodendrocytes?
Tumour necrosis factor
Which factors are neurotoxic and cause apoptosis of neuronal cells?
Platelet activating factor
Quinolinic acid
Nitric oxide
Some metabolites of arachidonic acid
Most common psychiatric presentation in AIDs?
HIV-related dementia
Depression
What % of HIV-infected patients present with psychosis?
10%
Which tissue volume is reduced in schizophrenia
Thalamus
Temporolimbic structures including hippocampus, amygdala and parahyppocampal gyrus
What happens to basal ganglia in schizophrenia?
Reduced volume, particularly in preneuroleptic area in catatonic patients.
Enlargement due to classic neuroleptics - reversed by atypicals
What is Heschl’s gyrus?
Primary auditory cortex
Neuronal density in schizophrenia?
Increased, may relate o observed decrease in neuronal size, with decreased dendritic arborisation and decreased neuropil compartment.
Any cell number or size change in schizophrenia?
Reduced numbers and size in affecting neurons in hippocampus and DLPFC
Pathological changes of Wernickes?
Degenerative changes including gliosis, small haemorrhages in third ventricle and aqueduct and cerebellar atrophy
Where is small haemorrhage seen in Wernickes?
Mamillary bodies
Hypothalamus
Mediodorsal thalamic nucleus
Cell count changes in autism?
Lower Purkinje cell count
Neocortex changes in Autism?
Inconsistent changes - increased cortical volume possibly related to reduced pruning
Pathological changes in Autism?
Hypoplasia of cerebellar vemis and cerebellar hemispheres
