Alzheimers and Epilepsy Flashcards
How does Alzheimer’s disease progress?
= a slow deterioration, starting from impairments in episodic memory, word finding, and topographical disorientation (which is due to HPC-entorhinal cortex damage, and occurs in 60% of cases).
How do we diagnose Alzheimer’s?
We use clock drawing, PET scans which show increased glucose, imaging Pittsburgh Compound-B (indicative of amyloid plaques) and volumetric MRIs.
What regions of the brain degenerate in Alzheimer’s?
The HPC, entorhinal cortex, neocortex etc.
What other macroscopic brain changes are seen in Alzheimer’s?
Cortical thinning, ventrical/sulci enlargement, reduced cerebral blood flow, and reduced glucose metabolism in the temporal lobes.
Tell me about amyloid plaques?
They are extracellular deposits, with a core of beta-amyloid, surrounded by degenerated axons/dendrives, microglia and astrocytes. T
Tell me about neurofibrillary tangles?
They are dying neurons, which contain accumulated twisted up filaments of hyperphosphorylated Tau protein. Normally, Tau proteins support microtubules, but when the proteins start to degenerate, microtubules collapse and become part of the tangles.
Where do we see the plaques and tangles first, and then where do they progress to?
We first see the plaques and tangles in the entorhinal cortex, then the HPC, and finally in the neocortex.
What is the myelination hypothesis of Alzheimer’s?
The myelination hypothesis posits that the extensive myelination that happens across life makes us vulnerable to things which lead to Alzheimer’s. Myelination follows a U shaped curve, whereby from 50y onwards neurons need remyelination faster than it can be done/repaired.
What does the myelination hypothesis explain?
It explains why there are non-random distributions of plaques and tangles: the neurons that show deposition of protein aggregates first are the ones which have long, thin axons which are myelinated later in development. It also explains why humans are the only creature to have AD — we are the only ones to myelinated in this way.
Finally, it explains why AD looks like ‘development/myelination in reverse’.
What is the cholinergic hypothesis of AD?
That the disease is a result of a deficit in online acetyltransferase, which synthesises ACh. If we have a deficit in that, there will be a deficit in ACh.
Is there any evidence for the cholinergic hypothesis of AD?
Not really – drugs up to ACh don’t really work very well, and it’s now thought that AD is more to do with HPC-cortical pathways, which are more related to glutamate.
Are there any key genes involved in familial AD?
Yup. Chromosome 21 has a gene that makes APP – having a mutation here leads to family AD.
Additionally, mutations to the presinilin (PS1/PS2) genes on chromosomes 1 and 14 cause defective beta-amyloid, contributing to plaques.
Are there any key genes involved in later-onset AD?
This is more tricky - it’s not as clear as early onset. A mutation in the gene for alipoprotein E has been suggested as a genetic cause. The E4 allele interferes with removal of long-form beta-amylase from the extracellular space, which would increase likelihood of beta-amyloid plaques.
