期刊
NEUROPATHOLOGY AND APPLIED NEUROBIOLOGY
卷 46, 期 7, 页码 722-734出版社
WILEY
DOI: 10.1111/nan.12664
关键词
Alzheimer's disease; LATE-NC; TDP-43; tau pathology
资金
- British Neuropathological Society
- Alzheimer's Society [AS-JF-18-01, AS-PG-16-010]
- Alzheimer's Research UK [ARUK-RF2018C-005]
- UK Medical Research Council [G0400074]
- Brains for Dementia research
- MRC [G0502157, G0400074, G0900652] Funding Source: UKRI
Aims Limbic-predominant age-related TDP-43 encephalopathy neuropathological change (LATE-NC) is present in approximately 50% of Alzheimer's disease (AD) cases and is associated with accelerated cognitive decline. Studies indicate a potential synergistic relationship between LATE-NC and hyperphosphorylated tau. It is unknown if LATE-NC is an independent driver of cognitive impairment or exerts its influence through synergistic relationships with tau. This cliniconeuropathological study investigated the impact of LATE-NC on quantified measures of AD-associated pathology and its impact on clinical measures. Methods A total of 61 AD cases underwent neuropathological assessment for LATE-NC and quantitative assessment [area covered by immunoreactivity (IR)] for early conformational tau (MC-1), late-stage hyperphosphorylated tau (AT8) and amyloid-beta in the amygdala and five neocortical regions. Clinical measures included age of disease onset, final Mini-Mental State Examination (MMSE) score and rate of cognitive decline. Results LATE-NC was present in 41 AD cases (AD/LATE-NC; 67.2%). No significant differences in MC-1-IR, AT8-IR or 4G8-IR were observed in any region between AD/LATE-NC and AD without LATE-NC, indicating no accelerated aggregation or hyperphosphorylation of tau proteins in the AD/LATE-NC cases. Final MMSE was significantly lower in AD/LATE-NC cases and was significantly associated with LATE-NC score even when controlled for the presence of both MC-1-IR and AT8-IR (P = 0.009). Conclusion The presence of LATE-NC in AD is not associated with an increase in the burden of early or late tau or A beta pathology. LATE-NC is associated with a lower final MMSE score independent of tau pathology.
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