Dementia: Neuropathology & Clinical Aspects Flashcards
Dementia disorders (4)
- Alzheimer’s disease
- Dementia with Lewy bodies
- Frontotemporal dementia
- Vascular dementia
Neuropathology of Dementia
- Microscopically
- Intra neuronal inclusion bodies
- Extra neuronal changes (p…)
- Macroscopically
- Generalised brain …
- Region specific … depending on dementia disorder
- Enlarged …
-
Microscopically
- Intra neuronal inclusion bodies
- Extra neuronal changes (plaques)
-
Macroscopically
- Generalised brain atrophy
- Region specific atrophy depending on dementia disorder
- Enlarged ventricles
Neuropathology of Dementia (2)
- … of proteins
- Abnormal …
- Neuroinflammatory environment
- Damaged neurons, cell …
- Protein involved:
- Amyloid, t…, s…
- Misfolding of proteins
- Abnormal accumulation
-
Neuroinflammatory environment
- Damaged neurons, cell death
-
Protein involved:
- Amyloid, tau, synuclein
Tau abnormalities
- … disease
- … dementia
- Alzheimer’s disease
- Frontotemporal dementia
Tau:
- Normal …
- Highly …
- Mostly found in …
- Mainly present in …
- Function: modulate stability of axonal microtubules, transport
- 6 isoforms -> 352-441 amino acid length (don’t need to know exactly)
- Disease -> … forms
- Leading to paired helical filaments (PHF)
- Neurofibrillary tangles (NFTs)
- PHFs -> NFTs -> Neurodegeneration
- Phosphorylation of tau is regulated by activated kinases
- … of tau can result in self-assembly of tangles of paired helical filaments (PHF)
- Normal protein
- Highly soluble
- Mostly found in brain
- Mainly present in axons
- Function: modulate stability of axonal microtubules, transport
- 6 isoforms -> 352-441 amino acid length (don’t need to know exactly)
- Disease -> hyperphosphorylated forms
- Leading to paired helical filaments (PHF)
- Neurofibrillary tangles (NFTs)
- PHFs -> NFTs -> Neurodegeneration
- Phosphorylation of tau is regulated by activated kinases
- Hyperphosphorylation of tau can result in self-assembly of tangles of paired helical filaments (PHF)
Tau:
- Normal protein
- Highly soluble
- Mostly found in brain
- Mainly present in axons
- Function: modulate stability of axonal microtubules, transport
- 6 isoforms -> 352-441 amino acid length (don’t need to know exactly)
- Disease -> hyperphosphorylated forms
- Leading to … helical filaments (PHF)
- … tangles (NFTs)
- PHFs -> NFTs -> …
- Phosphorylation of tau is regulated by activated …
- Hyperphosphorylation of tau can result in self-assembly of tangles of paired helical filaments (PHF)
- Normal protein
- Highly soluble
- Mostly found in brain
- Mainly present in axons
- Function: modulate stability of axonal microtubules, transport
- 6 isoforms -> 352-441 amino acid length (don’t need to know exactly)
- Disease -> hyperphosphorylated forms
- Leading to paired helical filaments (PHF)
- Neurofibrillary tangles (NFTs)
- PHFs -> NFTs -> Neurodegeneration
- Phosphorylation of tau is regulated by activated kinases
- Hyperphosphorylation of tau can result in self-assembly of tangles of paired helical filaments (PHF)
How can hyperphosphorylation of tau cause neurodegeneration?
results in self-assembly of tangles of paired helical fillaments - leading to neurofibrillary tangles - leading to neurodegeneration
What are Neurofibrillary tangles (NFTs)?
Neurofibrillary tangles (NFTs) are aggregates of hyperphosphorylated tau protein that are most commonly known as a primary biomarker of Alzheimer’s disease.
Neurofibrillary tangles (NFTs) are aggregates of … tau protein that are most commonly known as a primary biomarker of … disease.
Neurofibrillary tangles (NFTs) are aggregates of hyperphosphorylated tau protein that are most commonly known as a primary biomarker of Alzheimer’s disease.
Neurofibrillary tangles (NFTs)
- Described by alois Alzheimer
- Seen in neurons after staining
- Hamatoxylin
- Eosin
- Bielschowsky
- Bodian
- Congo red
- Most commonly found in temporal lobe structures
- …
- …
- Consist of … 10 nanometer diameter filaments twisted around each other in a helical manner (… helical filaments HF)
- Described by alois Alzheimer
- Seen in neurons after staining
- Hamatoxylin
- Eosin
- Bielschowsky
- Bodian
- Congo red
- Most commonly found in temporal lobe structures
- Hippocampus
- Amygdala
- Consist of paired 10 nanometer diameter filaments twisted around each other in a helical manner (paired helical filaments HF)
Amyloid
- Amyloid precursor protein (APP) is a transmembrane glycoprotein
- Broken down and eliminated in … brain
- APP is split by enzymes B-secretase then y-secretase (Gamma)
- B-amyloid is a peptide of 39-43 amino acids
- Most common forms are AB40 and AB42
- … is more common of the two, but … is the more fibrillogenic and is associated with disease states
- Fragments accumulate to form P…
- Build up of B-amyloid … cause neuronal damage
- Amyloid pathology - occurs outside neurons
- Amyloid precursor protein (APP) is a transmembrane glycoprotein
- Broken down and eliminated in normal brain
- APP is split by enzymes B-secretase then y-secretase (Gamma)
- B-amyloid is a peptide of 39-43 amino acids
- Most common forms are AB40 and AB42
- AB40 is more common of the two, but AB42 is the more fibrillogenic and is associated with disease states
- Fragments accumulate to form plaques
- Build up of B-amyloid plaques cause neuronal damage
- Amyloid pathology - occurs outside neurons
Amyloid
- Amyloid precursor protein (APP) is a transmembrane glycoprotein
- Broken down and eliminated in normal brain
- APP is split by enzymes B-secretase then y-secretase (Gamma)
- B-amyloid is a peptide of 39-43 amino acids
- Most common forms are AB40 and AB42
- AB40 is more common of the two, but AB42 is the more fibrillogenic and is associated with disease states
- Fragments accumulate to form plaques
- Build up of B-amyloid plaques cause neuronal damage
- Amyloid pathology - occurs outside neurons
- Amyloid precursor protein (APP) is a transmembrane glycoprotein
- Broken down and eliminated in normal brain
- APP is split by enzymes B-secretase then y-secretase (Gamma)
- B-amyloid is a peptide of 39-43 amino acids
- Most common forms are AB40 and AB42
- AB40 is more common of the two, but AB42 is the more fibrillogenic and is associated with disease states
- Fragments accumulate to form plaques
- Build up of B-amyloid plaques cause neuronal damage
- Amyloid pathology - occurs outside neurons
Amyloid - … is more common of the two, but … is the more fibrillogenic and is associated with disease states
Amyloid - AB40 is more common of the two, but AB42 is the more fibrillogenic and is associated with disease states
Frontotemporal dementia:
- … pathology
- Pick’s disease
- Pick bodies -rounded, microscopic structures found within neurons, aggregates of tau
- Hirano bodies
- Neurons swell, taking on a “ballooned” appearance. Hence called balloon cells
- Plaques and tangles are not found in Pick’s disease
- FTD is present in … and … temporal lobes
- Tau pathology
- Pick’s disease
- Pick bodies -rounded, microscopic structures found within neurons, aggregates of tau
- Hirano bodies
- Neurons swell, taking on a “ballooned” appearance. Hence called balloon cells
- Plaques and tangles are not found in Pick’s disease
- FTD is present in frontal and anterior temporal lobes
Synuclein abnormalities
- … disease
- Dementia with … bodies
- … aggregates of alpha-synuclein protein
- Parkinson’s disease
- Dementia with Lewy bodies
- Fibrillary aggregates of alpha-synuclein protein