Quantifying the accretion of hyperphosphorylated tau in the locus coeruleus and dorsal raphe nucleus: the pathological building blocks of early Alzheimer's disease.

Autor: Ehrenberg AJ; University of California, San Francisco, California, USA.; University of California, Berkeley, California, USA., Nguy AK; University of California, San Francisco, California, USA.; University of California, Berkeley, California, USA., Theofilas P; University of California, San Francisco, California, USA., Dunlop S; University of California, San Francisco, California, USA., Suemoto CK; University of São Paulo Medical School, São Paulo, Brazil., Di Lorenzo Alho AT; University of São Paulo Medical School, São Paulo, Brazil.; Hospital Israelita Albert Einstein, São Paulo, Brazil., Leite RP; University of São Paulo Medical School, São Paulo, Brazil., Diehl Rodriguez R; University of São Paulo Medical School, São Paulo, Brazil., Mejia MB; University of California, San Francisco, California, USA., Rüb U; University of Frankfurt, Frankfurt, Germany., Farfel JM; University of São Paulo Medical School, São Paulo, Brazil., de Lucena Ferretti-Rebustini RE; University of São Paulo, School of Nursing, São Paulo, Brazil., Nascimento CF; University of São Paulo Medical School, São Paulo, Brazil., Nitrini R; University of São Paulo Medical School, São Paulo, Brazil., Pasquallucci CA; University of São Paulo Medical School, São Paulo, Brazil., Jacob-Filho W; University of São Paulo Medical School, São Paulo, Brazil., Miller B; University of California, San Francisco, California, USA., Seeley WW; University of California, San Francisco, California, USA., Heinsen H; University of São Paulo Medical School, São Paulo, Brazil.; University of Wüerzburg, Wüerzburg, Germany., Grinberg LT; University of California, San Francisco, California, USA.; University of São Paulo Medical School, São Paulo, Brazil.
Jazyk: angličtina
Zdroj: Neuropathology and applied neurobiology [Neuropathol Appl Neurobiol] 2017 Aug; Vol. 43 (5), pp. 393-408. Date of Electronic Publication: 2017 Mar 31.
DOI: 10.1111/nan.12387
Abstrakt: Aims: Hyperphosphorylated tau neuronal cytoplasmic inclusions (ht-NCI) are the best protein correlate of clinical decline in Alzheimer's disease (AD). Qualitative evidence identifies ht-NCI accumulating in the isodendritic core before the entorhinal cortex. Here, we used unbiased stereology to quantify ht-NCI burden in the locus coeruleus (LC) and dorsal raphe nucleus (DRN), aiming to characterize the impact of AD pathology in these nuclei with a focus on early stages.
Methods: We utilized unbiased stereology in a sample of 48 well-characterized subjects enriched for controls and early AD stages. ht-NCI counts were estimated in 60-μm-thick sections immunostained for p-tau throughout LC and DRN. Data were integrated with unbiased estimates of LC and DRN neuronal population for a subset of cases.
Results: In Braak stage 0, 7.9% and 2.6% of neurons in LC and DRN, respectively, harbour ht-NCIs. Although the number of ht-NCI+ neurons significantly increased by about 1.9× between Braak stages 0 to I in LC (P = 0.02), we failed to detect any significant difference between Braak stage I and II. Also, the number of ht-NCI+ neurons remained stable in DRN between all stages 0 and II. Finally, the differential susceptibility to tau inclusions among nuclear subdivisions was more notable in LC than in DRN.
Conclusions: LC and DRN neurons exhibited ht-NCI during AD precortical stages. The ht-NCI increases along AD progression on both nuclei, but quantitative changes in LC precede DRN changes.
(© 2017 British Neuropathological Society.)
Databáze: MEDLINE
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