期刊
ANNALS OF NEUROLOGY
卷 84, 期 5, 页码 741-753出版社
WILEY
DOI: 10.1002/ana.25344
关键词
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资金
- NIH [P50 AG05681, P01 AG03991, P01 AG26276]
- Coins for Alzheimer's Research Trust
- Alzheimer's Drug Discovery Foundation
- Astellas Foundation of Research on Metabolic Disorders
- Mochida Memorial Foundation for Medical and Pharmaceutical Research
- NATIONAL INSTITUTE ON AGING [P01AG003991, P50AG005681, P01AG026276] Funding Source: NIH RePORTER
Objective Methods To characterize the pattern of neuron loss in hippocampal sclerosis of aging (HS-Aging) and age-related diseases and to evaluate its contribution to cognitive impairment in the elderly. Participants (n = 1,361) came from longitudinal observational studies of aging at the Knight Alzheimer Disease Research Center, Washington University (St. Louis, MO). Relative neuron loss in the hippocampus of HS-Aging was measured using unbiased stereological methods. Transactive response DNA-binding protein of 43 kDa (TDP-43) proteinopathy, a putative marker of HS-Aging, was assessed. Clinical and cognitive data were analyzed using parametric statistical methods. Results Interpretation Ninety-three cases had HS-Aging (6.8%), 8 cases had pure HS-Aging, and 37 cases had comorbid intermediate or high Alzheimer's disease neuropathological change (i/h ADNC). Relative neuron loss (ratio of neuron number in hippocampal subfield CA1 to the neuron number in parahippocampal gyrus) was 0.15 for HS-Aging; this was significantly lower than 0.64 for i/h ADNC and 0.66 for control cases (Kruskal-Wallis test, p < 0.0001; p = 0.0003, respectively). TDP-43 proteinopathy was present in 92.4% of HS-Aging cases, higher than that in i/h ADNC (52%) and control (25%) cases. Pure HS-Aging cases were more likely to have cognitive impairment in the memory domain. Relative neuron loss in the hippocampus compared to the parahippocampus gyrus may be useful in distinguishing HS-Aging in the context of comorbid ADNC. HS-Aging contributes to cognitive impairment, which phenotypically resembles AD dementia. TDP proteinopathy is a frequent comorbidity in HS-Aging and may contribute to cognitive impairment to a modest degree. Ann Neurol 2018;84:749-761
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