期刊
JOURNAL OF ALZHEIMERS DISEASE
卷 35, 期 1, 页码 199-212出版社
IOS PRESS
DOI: 10.3233/JAD-121255
关键词
Alzheimer's disease; APP; atrophy; autosomal dominant; magnetic resonance imaging; PSEN1
资金
- Department of Health's NIHR in Dementia
- NIHR Dementias and Neurodegenerative Disease Research Network (DeNDRoN)
- Alzheimer's Research UK
- Wellcome Trust [091593/Z/10/Z]
- Medical Research Council UK
- UK Medical Research Council [G9626876]
- MRC Bioinformatics Training Fellowship [G90/86]
- Alzheimer's Research UK Research Fellowships (UK)
- MRC Clinical Research Training Fellowship [G0900421]
- TSB [M1638A]
- CBRC [168]
- EPSRC
- Alzheimer Research UK
- HEFCE
- Wellcome Trust Senior Clinical Fellowship
- MRC Senior Clinical Fellowship [G116/143]
- Alzheimers Research UK [ARUK-Network2011-6-ICE] Funding Source: researchfish
- Medical Research Council [MC_U123160651, G90/86, G0601846, G0900421, G116/143] Funding Source: researchfish
- National Institute for Health Research [NF-SI-0508-10123] Funding Source: researchfish
- MRC [G0900421, G116/143, G90/86, G0601846, MC_U123160651] Funding Source: UKRI
Mutations in the presenilin1 (PSEN1) and amyloid beta-protein precursor (APP) genes account for the majority of cases of autosomal dominantly inherited Alzheimer's disease (AD). We wished to assess and compare the patterns of cerebral loss produced by these two groups of mutations. Volumetric magnetic resonance imaging and neuropsychological assessments were performed in individuals with clinical AD carrying mutations in the APP (n = 10) and PSEN1 (n = 18) genes and in healthy controls (n = 18). Voxel-based morphometry (VBM), cortical thickness, and region of interest analyses were performed. Mini-Mental State Examination scores were similar in the two disease groups suggesting similar levels of disease severity. There was evidence that APP subjects have smaller hippocampal volume compared with PSEN1 subjects (p = 0.007), and weak evidence that they have larger whole-brain and grey matter volumes (both p = 0.07). Although there was no evidence of statistically significant differences between APP and PSEN1 in VBM or cortical thickness analyses, effect-maps were suggestive of APP subjects having more medial temporal lobe atrophy and conversely PSEN1 subjects showing more neocortical loss. Neuropsychological data were consistent with these regional differences and suggested greater memory deficits in the APP patients and greater impairment in non-memory domains in the PSEN1 group, although these differences were not statistically significant. We conclude that the mechanisms by which APP and PSEN1 mutations cause neuronal loss may differ which furthers our understanding of the neuropathology underlying AD and may inform future therapeutic strategies and trial designs.
作者
我是这篇论文的作者
点击您的名字以认领此论文并将其添加到您的个人资料中。
推荐
暂无数据