Neuropathology of Dementia Flashcards
Identify the protein involved in each disease process (tau, β-amyloid, α-synuclein, PrPp, etc).
alpha synuclein are known as lewy bodies, they have a eosinophilic core surrounded by pale halo, found in the substantia nigra in parkinson’s disease, and they are also seen in the cortex in dementia with lewy bodies
Describe the specific microscopic findings associated with each disease process (NFTs, amyloid plaques, inclusions, spongiform change, etc).
Neuritic plaques, Aβ peptides aggregate in tissue as β-pleated sheets (amyloid), eliciting a toxic response in astrocytes and microglia
Hyperphosphorylated tau protein is also present in AD
Picks: Neuronal loss and gliosis of outer layers of cortex, caudate nucleus, thalamus
Gliosis of subcortical white matter
Spongiform change
Pick bodies
Intracytoplasmic inclusions
Tau+
“Pick bodies” viewed with Bielschowsky silver stain
Identify the genes involved in familial forms of Alzheimer’s disease.
Early: APP gene, Presenilin-1, Presenilin-2; late: ApoE ε4 alleles (chr 19)
Define prions and describe the mechanism by which they induce prion diseases.
Abnormal form facilitates conformation change in normal PrP molecules, which accumulate in the tissue Normal conformation (PrPc) is -helix, which is changed to -pleated sheet in disease state (PrPp)
Recognize the symptoms of Wernicke’s encephalopathy, and describe the etiology and treatment.
Clinical syndrome: Delirium Gait ataxia Nystagmus Alcoholism or other settings associated with poor nutrition TREAT: Thiamine (B1) deficiency Treat with parenteral thiamine In thiamine-deficient patients, giving glucose without thiamine can precipitate Wernicke’s encephalopathy
Recognize a wide variety of disease processes that can produce dementia-like symptoms (vascular dementia, metabolic disorders, brain tumors, etc).
HIV
Neurosyphilis
Cryptococcal meningitis
Whipple’s disease
Prion diseases
Progressive multifocal leukoencephalopathy (PML)
Subacute sclerosing panencephalitis (SSPE)
A 40 year old male with Down’s syndrome has symptoms of advanced dementia consistent with Alzheimer’s disease. Why is early onset Alzheimer’s disease common in Down’s syndrome?
the amyloid precursor protein (APP) is located on chromosome 21
Patients with FTDP-17 have which of the following brain abnormalities?
Extensive deposition of intracellular hyperphosphorylated tau protein in neurons and glia
T/F: HIV encephalopathy is frequently treated with HAART therapy
HIV associated dementia persists DESPITE HAART therapy:
Microglial nodules and TEST: multinucleated giant cells near blood vessels
Involves white matter, diencephalon, and brainstem
In AD: APP amyloid precursor protein gene is on____
In familial AD there are two types: ____ and _____, the genes responsible for early onset are :
The genes responsible for late onset are:
chromosome 21; app gene, presenilin 1, and presenilin 2; apoE E4 alleles chromosome 19: most common form of familial AD
The atrophy is typically more pronounced in the ______
The atrophy is typically more pronounced in the medial temporal lobes
Neuritic plaques
Composed of dystrophic neurites and mitochondria
Astrocytes and microglia associated with amyloid fibrils with a central core of -amyloid
neuritic plaques tend to aggregate and be distributed in the _________, but you don’t see them in:
hippocampus, medial cortex, posterior cingulate gyrus, association cortex; not in motor cortex (hence why you don’t see a lot of sensory motor deficits in patients
neurofibrillary tangles:
hyper-phosphorylated tau proteins; difficult to break down and can persist as “ghosts” after neuron dies (and is visible with bielschowsky silver stain)
Pick’s Disease is characterised by:
Neuronal loss and gliosis of outer layers of cortex, caudate nucleus, thalamus Gliosis of subcortical white matter Spongiform change Pick bodies Intracytoplasmic inclusions Tau+
FTDP-17 is characterised by:
Extensive deposition of intracellular hyperphosphorylated tau protein in neurons and glia
TEST: Pick’s Disease is characterised by:
Neuronal loss and gliosis of outer layers of cortex, caudate nucleus, thalamus Gliosis of subcortical white matter Spongiform change Pick bodies Intracytoplasmic inclusions Tau+
Cortical Lewy bodies are seen in ______
Cortical Lewy bodies are seen in Dementia with Lewy Bodies, not Parkinson’s Disease.
vascular dementia is characterised by:
2nd most common cause of dementia in the elderly
Cardiac issues, history of stroke, etc
Preventable by treating predisposing conditions: May also be classified as: Cortical Subcortical Lacunar
vascular dementia is characterised by:
2nd most common cause of dementia in the elderly
Cardiac issues, history of stroke, etc
Preventable by treating predisposing conditions: May also be classified as: Cortical Subcortical Lacunar
Neurosyphilis:
Rod-shaped microglia on silver stain (SILVER STAIN MENTIONED CONSTANTLY!)Other symptoms – myoclonus, ataxia, visual abnormalities, mutism
CJD is characterised by:
myoclonus, ataxia, visual abnormalities, mutism
Lewy Bodies are:
Positive for alpha-synuclein, and have a:
Eosinophilic core surrounded by pale halo
Found in Substantia nigra in Parkinson’s disease
Also seen in the cortex in Dementia with Lewy bodies
TEST: Wernicke’s Encephalopathy: caused by ____- and presents with _____
Thiamine B1 deficiency, and presents with Delirium, gait ataxia, nystagmus (result of alcoholism)
CJD is characterised by;
CSF: 14-3-3 protein
Rapid progression
(death in usually in less than 1 year)
myoclonus, ataxia, visual abnormalities, mutism
with CJD, the patient would present with ________
abnormal EEG,
Neurosyphilis presents histologically with:
rod-shaped microglia on silver stain
HIV Encephalopathy presents on histo with:
microglial nodules and multinucleated giant cells near blood vessels
AD on histo has:
dystrophic neurites and mitochondria; the astrocytes and microglia associated with amyloid fibrils with a central core of B-amyloid
CJD on histo presents with;
spongiform change and amyloid plaques in cerebellum
Wernicke’s encephalopathy presents with:
hermorrhage, neuronal loss, and gliosis in mammillary bodies and periventricular area around the third and fourth ventricles
Wernicke’s encephalopathy clinically presents with:
Delirium Gait ataxia Nystagmus Alcoholism or other settings associated with poor nutrition Thiamine (B1) deficiency
Wernicke’s encephalopathy with confabulation points to:
korsakoff! It is a results of wernicke’s
