Neuropathology Flashcards
(35 cards)
Synucleinopathies
DLB
PD
MSA (multiply stem atrophy)
Tauopathies
Alzheimer's Picks PNPalsy CBD Frontotemporal dementia with Parkinsonism
Alzheimer’s findings
Diffuse global atrophy
Flattened cortical sulci
Enlarged cerebral ventricles
AMYLOID PLAQUES, NEUROFIBRILLARY TRIANGLES IN NEOCORTEX AND E4 allele
Early onset Alzheimer’s linked to Beta-APP (long arm of chromosome 21)
Binswangers
Type of vascular dementia (vascular dementia primarily affects small and medium sized vessels)
Aka Subcortical Arteriosclerotic Encephalopathy
Many small infarctions of white matter (sparing cortical regions)
Subcortical LEUCOMALACIA
CJD
No gross morphological changes as short duration diseases
Histologically vacuolisation
Frontotemporal Dementia
Frontal and Temporal Atrophy
Mutation in Tau Protein
Parkinson disease
LRRK2 explains up to 7% of familial cases
Alpha Synuclein deposits.
Marcospocially: depigmentation of SN (zona compacta ) and locus coreleus, diffuse cortical atrophy
Histologically: reactive ASTROCYTES, neurone loss, lb in sn/locus Coreleus/dorsal motor nucleus of vagus/hypothalamus/nucleus basalis meynert/raphe nuclei/edinger-Westphal nucleus.
Ascending and descending tracts
Anterior spinothalamic tract: light tough and pressure
Lateral spinothalamic tract: pain and temperature
Anterior posterior spinocerebllar tract: proprioception/pressure/touch
Lateral corticospinal: voluntary movements
CJD
Macroscopic: no characteristic signs, generalised cereal atrophy
Microscopic: spongiform encephalopathy, microcysts, neuronal loss, gliosis
Normal Prion Protein PrPc converted into PrPsc which is protease resistant and accumulates in the CNS > cerebral cortex degeneration
14-3-3 is an abnormal protein found in CNS by immunoassay (can also be found in stroke and viral encephalitis)
Most useful diagnostic test in variant CJD is MRI (FLAIR) > PULVINAR SIGN IN 90% in posterior thalamic region.
Hirano bodies
Rod shaped eosinophilic bodies in cytoplasm of Neurons, intra cellular aggregates of actin and non-actin associated proteins.
ALZEIMER’S DEMENTIA
Cerebral amyloid angiopathy
- Accumulation of ABeta in cerebral cortex blood vessels and overlying leptomeninges.
- 30% normal elderly, > 90% Alzeimers patients
- Can cause CVA mostly haemorrhagic
NEUROFIBRILLARY tangles
ALZEIMERS DISEASE
ABNORMALLY PHOSPHORYLATED TAU PROTEIN
First appear in HIPPOCAMPUS, faintly basophilic, as dementia develops they go to other cortical areas such as hypothalamus/thalamus
Tau is needed for microtubule assembly
Beta A4 interacts with cholinergic receptors and this stimulates abnormal phosphorylation of tau.
Can be identified via staining with antibody.
Can also occur in Downs, Dementia Pugilistica, Parkinson dementia complex of Guam, normal elderly.
Braak and Braak Stage: V-VI is AD
IF PLAQUES + TANGLES = significant cognitive decline
Synaptophysin
Best correlate of decline is number of synapses.
Marker for synapses = SYNAPTOPHYSIN a protein found I. The presynaptic endings
LBD
Lewy Bodies = weakly eosinophilic, spherical, cytoplasmic inclusions
In Parkinson’s only in SN, in DLB all over including temporal lobe,cingulate Gyrus,frontal lobes.
Those outside of SN are less eosinophilic, and lack clear halo.
No simple correlation between number of lb and cognitive decline
Antibody for detection: UBIQUITIN
STAINING: alpha synuclein can also detect lb.
Alpha synuclein accelerates dopamine reuptake (this can be toxic)
Lewy NEURITES:’Nerve cell processes containing alpha synuclein, mostly in CA2/3 of hippocampus and SN. Can occur in PD or DLB.
MICROVALUATION: cerebral cortex, mainly medial temporal regions.
FRONTO-TEMPORAL DEMENTIA
Three types:
- frontal lobe degeneration type, spongiform degeneration of layers III and V, loss of large cortical nerve cells.
- Picks, Frontotemporal atrophy, abundant gliosis, Picks bodies (cytoskeletal elements, argentophilic tau and ubiquitin reactive inclusions), swollen neuronal cells e loss of Nissl substance oval shape and displaced nucleus Pick Cells
- Motor neurone disease type: loss of large nerve cells, microvaluation, mild gliosis. Ubiquitin inclusions in frontal cortex and hippocampus. Pathology in ANTERIOR HORN.
CJD
Three types.
Sporadic (most common)
Familial
Variant (bovine)
If a person lives beyond 6 months there may be cerebral atrophy.
Microscopically: spongiform encephalopathy, due to vacuolisation, vacuoles coalesce to microcysts. Neuronal loss, gliosis.
Polymorphism at Codon 129 of PrP may make susceptible to CJD. Amino acid methionine or valine may be present. 73% with sporadic CJD have M/M phenotype, 100% vCJD have M/M phenotype.
Huntingtons dementia
- Loss of Neurons in cerebral cortex, in caudate and putamen, and subsequent astrocytosis.
- Protein deposits form nuclear inclusions in Neurons.
- Marked atrophy of corpus striatum especially Head of caudate shrinks, and “ex vacuo” dilatation of anterior horns of lateral ventricles.
- Marked atrophy of cc especially frontal lobe gyri
- Dilation of 3rd and Lateral ventricles
- Small brain reduced mass.
Schizophrenia
Decrease brain weight, brain length, volume of cerebral hemispheres
Enlargement of lateral ventricles
Decreased volume thalamus, hippocampus, amygdala, Parahippocampal Gyrus
White mater reductions hippocampus and Parahippocampal Gyrus
Increased incidence of cavum septi pellucidi
Left temporal horn enlargement
Schizophrenia Histologically changes
Hippocampus DLPFC recused cell numbers/size
Increased neurone density
CA3-CA4 cellular disarray
Deferments in presynaptic markers ?reduced number of synapses (excessive synaptic pruning theory)
Gulatamatergic synapses may be especially vulnerable in hippocampus and DLPFC, predominantly GABAergic involvement in cingulate Gyrus.
Alcohol brain damage
Wernickes: gliosis and small haemorrhages in 3rd ventricle and aqueduct (mammillary body, hypothalamus, colliculi, midbrain tegmentum) and cerebral atrophy.
Brain: Shrinkage and loss of white matter, some is reversible.
Neuronal loss in superior frontal association cortex, hypothalamus (supraoptic and para ventricular nuclei) and cerebellum. “SHC”
Mood disorders
WMH in Subcortical grey matter, basal ganglia, periventricularly.
Seen in excess in bpad and unipolar depression.
In major depression, they are common in elderly linked to vascular disease.
Wmh means poor prognosis.
Lithium can increase cortical grey matter, neurogenesis and apoptosis
ADs regenerate monoaminergic axons, promot neurogenesis, and prevent loss of dendritic spines in some animals.
APs alter synaptic and neuronal morphology esp in CAUDATE/putamen, and may increase glial density in PFC.
Autism
Hypoplasia of cerebellar vermis
Lowered Purkinje cell count in cerebellum
HIV
Hiv receptors are CD4 and CD8, hiv co receptors are CXCR4 and CCR5
Manor route of entry are CD4+ helper T lymphocytes and monocytes
Strains from brain infect more macrophages (mutation GP120) than lymphocyte
Entry into BBB “Trojan Horse Hypothesis”
All main cell types of CNS can be infected. Macrophage and microglia most commonly > neurodegenerarion occurs by shedding of viral proteins and releasing cytokines and neurotoxins into CNS > tat and TNf-alpha contribute to disruption of BBB which then becomes more permeable to infected monocytes and cytokines in the periphery.
HIV
Macrophages become infiltrated > micro glial nodules form > multinucleated giant cells from fusion of microglia and macrophages in central white and deep gray matter > ASTROCYTES activate and damage > neuronal loss hippocampus, BG, Caudate > white matter pathology and myelin damage > lipid macrophages (severe) > presence HIV-1 in CSF
