Naslov
Tau hyperphosphorylation and entorhino-hippocampal neuron loss in Alzheimer's disease

Autori
Šimić, Goran

Vrsta, podvrsta i kategorija rada
Sažeci sa skupova, sažetak, stručni

Izvornik
SISSA Conference 2001: Neurobiology in Eastern and Western Europe / - Trst : International School for Advanced Studies, 2001

Skup
Neurobiology in Eastern and Western Europe

Mjesto i datum
Trst, Italija, 30.11.2001. - 03.12.2001

Vrsta sudjelovanja
Pozvano predavanje

Vrsta recenzije
Međunarodna recenzija

Ključne riječi
tau protein; hyperphosphorylation; Alzheimer's disease; entorhinal cortex; hippocampus

Sažetak
The most characteristic neuropathological change in Alzheimer's disease (AD) is the degeneration of neuronal cytoskeleton that can be seen at the light-microscopical level as neurofibrillary tangle (NFT), neuropil thread (NT) or neuritic component of neuritic plaques. In the preclinical stage of AD, NFT and NT start to develop selectively in the projection neurons of the upper layers of the transentorhinal and entorhinal cortices and then unequivocally spread onto hippocampal formation. The hyperphosphorylated tau protein shown by the AT8 antibody represents an early cytoskeleton change which eventually leads to the formation of argyrophilic NFT and NT. The purpose of author's long-term study has been to quantitate the extent of neurofibrillary changes and neuron loss in patients with sporadic AD and cognitively intact elderly control subjects. All of the brains analyzed were staged for neurofibrillary changes and extracellular beta-amyloid deposits according to Braak and Braak. So far, by using optical disector method, neuron loss related to normal aging was evaluated from estimates of the total number of neurons in each of the major hippocampal subdivisions and entorhinal cortex layers II and III of 30 normal subjects ranged in age from 16 to 99 years. The AD related losses were evaluated from data obtained from 25 cases of AD and 22 age matched controls, while the number of neurons containing neurofibrillary pathology was quantified in 12 AD and 12 control subjects. The results showed that, when taken into account only the data obtained by silver staining, a part of neuron loss in the entorhinal cortex and hippocampus in AD may seem to precede in time and exceed the quantity of NFT. However, when neurons with initial neurofibrillary changes that were stained and counted on adjacent sections (so-called group 2 AT8-immunoreactive neurons, which cannot be readily seen by silver staining) were added to the counts of classic and 'ghost' NFT, all of the observed neuron loss could be explained by the neurofibrillary pathology. These data suggest that tau hyperphosphorylation is the major cause of entorhino-hippocampal neuron loss in AD.

Izvorni jezik
Engleski

Znanstvena područja
Kliničke medicinske znanosti

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