Why is the Beta-amyloid plaque accumulation higher in lacunosum molculare and dentate gyrusthan than other parts of the brain in Alzheimer's patients?
The link below may be useful for answering to your question, which is a very interesting one. Good luck...
http://www.ncbi.nlm.nih.gov/pubmed/24376398
Dear Balaji. This is probably due to the fact that there's a higher density of microvessels in these area esp in SLM. There's increasing evidence that Alz dis is caused by breakdown of small vessels and this leads to hypoxia, oxidative stress and increased oligomerisation and aggregation of Abeta. As Abeta has high affinity to free haem, Abeta plaques occur mainly where vessels breakdown. This is the other reason of selective vulnerability of hippocampus vs other areas of the brain where AD first develops. There are several papers in the field in the last decade to highlight this. In particular take a look at the paper by Stone 2008 in Medical Hypothesis.
Not sure about the early onset plaque pathology in the hippocampus in AD. While true for NF tangles, which in forebrain starts somewhere in the entorhinal areas, the earliest targets of plaque pathology in humans are associative areas in the neocortex and later only in allocortical structures (e.g. Braak, Mesulam and other papers).
Dear Balaji,
Ab is known to be traficked anterograde and retrograde along axons (Bayer T.A., Brain pathol. 2001). A defect in these „normal” metabolism or an increased production in the neuron’s body might lead to abnormally high Ab being released around the synapses.
And indeed, it has been shown that NFT do tend to occur first in the enthorinal cortex, while amyloid plaques tend to occur afterwards in the dentate gyrus in the hyppocampus. The main afference of the hippocampus comes with fibers from the enthorinal cortex passing through the subicular formation [either to the dentate gyrus (the perfornat pathway) or directly to the CA3 area of the hyppocampus]. These together might mean that the impairment of the pyrmaidal cells in enthorinal cortex (NFTs are there first) might favorise Ab release along their axonal boutons, which would be mostly in the dentate gyrus.
I hope it helps,
All the best,
Daniel
To look at a different angle, considering the Metallostasis part of AD's pathology I think in the specified regions, there is a disruption in metal cation homeostasis. As Sivaraman said, the higher microvascular density may play an important role upon their
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