6/3- Neuropathology of Dementia Flashcards Preview

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Flashcards in 6/3- Neuropathology of Dementia Deck (39):

Key feature (anatomical) of dementia?

Cortical degeneration


Causes of cortical degeneration?

- Alzheimer's dz

- Pick's dz (frontotemporal dementia)

- Lewy body dementia

These are the 3 MCCs of neurodegenerative dementia (each have varied initial symptoms)


What does this show? 

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Cortical atrophy

(Left side shows caudate atrophy and hydrocephalus ex vacuo of Alzheimer's dz?)

(Right side shows frontotemporal degeneration/Pick's disease; selective in frontal and temporal regions)


2 categories of dz within Alzheimer's?




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2 categories of disease within Non-Alzheimer's neurodegenerative diseases with dementia?

Tauopathies (PSP):

- FTD complex/Pick's dz

Synucleinopathies (PD, LBD):

- Lewy Body Complex 

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What is seen microbiologically in Alzheimer's dz?

- Beta-amyloid (extracellular) + Tau (intracellular)


What is seen microbiologically in Pick's dz/FTLD?

- Tauopathy (pure)


seen microbiologically in Lewy Body Dementia (LBD)?

- Alpha synuclein


Where does atrophy start in Alzheimer's?

Starts in amygdala, hippocampus, and temporal lobe


Neuronal changes in Alzheimer's?

- Loss of cortical cholinergic innervation

(Central) cholinesterase inhibitors now in clinical use in mild-moderate cases


Characteristics of Alzheimer's dz (symptoms)?


- Starts with short-term memory

- Onset may be subtle

- Early onset cases are typically genetic


What anatomical features are seen grossly with Alzheimer's?

Cortical atrophy and hydrocephalus ex vacuo

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Histological features of Alzheimer's dz?

- Neuritic plaques- EXTRAcellular

- Neurofibrillary trangles- INTRAcellular

- Amyloid deposition in mature neuritic plaques and in the walls of cortical and leptomeningeal blood vessels

- Many people believe that the plaques (beta-amyloid) are the initiating event and the tangles (hyperphosphorylated tau) are 2ndary

- AD therefore is a beta-amyloidopathy


What is this?

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Plaques and tangle seen in Alzheimer's dz

- Silver stain binding proteins rich in B-sheets and fibrillogenesis Seen center left is a plaque (extracellular)

- Black structures are axons adjacent to deposition of B-amyloid; stuff like tau begins to accumulate within the processes

- Most of the plaque is comprised of B-amyloid with neuroprocesses with accumulations of tau

Seen center right is a process with accumulation of tau (tangle?)


CERAD plaque estimation in Alzheimer's dz (picture)

Few, moderate, or many 

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What is this? 

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Neurofibrillary tangles in Alzheimer's dz (deposition of tau)

- When tau is deposited in this way, it becomes hyperphosphorylated


Plaque staging or counting has a ____ (good/poor) correlation with dementia. Tangle staging has a ___ (good/poor) correlation with dementia.

Plaque staging or counting has a poor correlation with dementia (HOW MANY PLAQUES)

Tangle staging has a good correlation with dementia (WHERE ARE THE TANGLES)


Progression of Alzheimer dz (main steps)?

- Pre-symptomatic

- Mild cognitive impairment (MCI)

- Alzheimer's dz


Progression of Alzheimer's: Pre-symptomatic?

The pt has no cognitive impairment.

There is growing evidence that EC beta-amyloid is accumulating and tangles are beginning to form, esp in the hippocampus and adjacent temporal cortex


Progression of Alzheimer's: Mild cognitive impairment (MCI)?

The pt has mild deterioration of memory and cognitive function that worries the patient but which does not interfere with daily living


Progression of Alzheimer's: Alzheimer's dz?

These individuals are frankly demented on clinical examination, neuropsychological evaluation and there is impairment of activities of daily living


T/F: Alzheimer's plaques can grow overnight


Study with mice has shown that they can grow significantly overnight


Timeline of plaque development/growth in Alzheimer's?

Plaques form in a day; macrophages/microglia react within a couple days; neurotic processes form within days

- Day 1: microplaque

- Day 2: distended neurites, amyloid-B-oligomer, astroglia and microglia first appear

- Day 3: dystrophic neurites

- Day 7: mature plaque

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How many people with MCI will go on to develop Alzheimer's?

Roughly 1/2


What is this?

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Amyloid angiopathy in Alzheimer's dz

- Beta amyloid in vascular walls (typically cleared in blood, but if excessive accumulation in EC space, can build up in vessel wall -> fragility and IC hemorrhaging)


What is Pick's disease? Key clinical features?

Frontotemporal dementia

- Uncommon severe dementing dz Symptoms


-(rare cases of new artistic/musical abilities)


Micro anatomical features of Pick's disease?


- Neuronal loss and gliosis

- Ballooned neurons

- NO plaques, tangles, or granulovacuolar

- Faintly basophilic intraneuronal cytoplasmic inclusions (Pick bodies) immunoreactive for tau

Pick's is a pure TAUOPATHY


Gross anatomical features of Pick's disease?


- Marked temporal and frontal atrophy

- "Knife edge" gyri

- Sparing of post 2/3 of superior temporal gyrus, parietal lobes, and precentral (motor) gyrus


What is this?

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Cortical atrophy seen in Pick's disease (Frontotemporal Atrophy

) - so thin gyri that they look like "knife edge"


What is this?

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Pick bodies in Pick's dz


What is this? 

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Tau inclusions: Globose tangles in PSP

- Silver stain


What is this?

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Tau inclusions: Pick bodies in Pick's dz

- Silver stain; Pick bodies are the larger blots while nuclei are smaller


What is this?

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Neuronal loss, gliosis, rarefaction in Pick's dz

- Rarefied = not many neurons; a lot of open space

- Notice: no plaques (unlike AD)


What is seen micro in Lewy Body Dz?

- Subtle eosinophilic cytoplasmic inclusions in cortical neurons (Lewy bodies)

- Difficult to identify on H&E; immunopositive with alpha-synuclein


What is the most common cause of dementia? 2nd most common cause?

1st: Alzheimer's disease

2nd: Lewy Body disease


Clincical features of Lewy Body disease?

- Fluctuating cognitive features (starkly different from day to day!)

- Visual hallucinations (often well-formed, cartoon-like; pt is aware that they are hallucinating)

- Extrapyramidal features may occur (e.g. some features of Parkinsonism)


What is this?

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UL: Parkinson's disease (loss of SN)

UR: Lewy bodies in pigmented neurons with central core and halo

LL: Lewy body

LR: Cortical Lewy Bodies

(PD and LBD are synucleinopathies)


What is this?

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Cortical Lewy Bodies

- a-synuclein

(Parkinson's dz and Lewy body dementia are synucleinopathies)


Pharmacological approaches?

Central cholinesterase drugs

- Donepezil

- Rivastigmine

- Galanthamine

Glutaminergic neurotransmission modulators  (use any place there' degeneration and a lot of glutamate buildup)

- Riluzole (for ALS)

- Memantine (for Alzheimer's)

Parkinsonism Sx (in LBD) may be treatable with DA, but cost may exceed therapeutic benefit