Quantifying the accretion of hyperphosphorylated tau in the locus coeruleus and dorsal raphe nucleus: the pathological building blocks of early Alzheimer's disease
AJ Ehrenberg, AK Nguy, P Theofilas… - Neuropathology and …, 2017 - Wiley Online Library
Neuropathology and applied neurobiology, 2017•Wiley Online Library
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 …
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 …
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.
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