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Impact of apolipoprotein ɛ4–cerebrospinal fluid beta‐amyloid interaction on hippocampal volume loss over 1 year in mild cognitive impairment
Author(s) -
Chiang Gloria C.,
Insel Philip S.,
Tosun Duygu,
Schuff Norbert,
TruranSacrey Diana,
Raptentsetsang Sky T.,
Thompson Paul M.,
Reiman Eric M.,
Jack Clifford R.,
Fox Nick C.,
Jagust William J.,
Harvey Danielle J.,
Beckett Laurel A.,
Gamst Anthony,
Aisen Paul S.,
Petersen Ron C.,
Weiner Michael W.
Publication year - 2011
Publication title -
alzheimer's and dementia
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 6.713
H-Index - 118
eISSN - 1552-5279
pISSN - 1552-5260
DOI - 10.1016/j.jalz.2010.12.010
Subject(s) - cerebrospinal fluid , hippocampal formation , amyloid beta , amyloid (mycology) , apolipoprotein e , cognitive impairment , beta (programming language) , medicine , cognition , neuroscience , psychology , endocrinology , pathology , computer science , disease , programming language
Background The majority of studies relating amyloid pathology with brain volumes have been cross‐sectional. Apolipoprotein ɛ4 ( APOE ɛ4), a genetic risk factor for Alzheimer's disease, is also known to be associated with hippocampal volume loss. No studies have considered the effects of amyloid pathology and APOE ɛ4 together on longitudinal volume loss. Methods We evaluated whether an abnormal level of cerebrospinal fluid beta‐amyloid (CSF Aβ) and APOE ɛ4 carrier status were independently associated with greater hippocampal volume loss over 1 year. We then assessed whether APOE ɛ4 status and CSF Aβ acted synergistically, testing the significance of an interaction term in the regression analysis. We included 297 participants: 77 cognitively normal, 144 with mild cognitive impairment (MCI), and 76 with Alzheimer's disease. Results An abnormal CSF Aβ level was found to be associated with greater hippocampal volume loss over 1 year in each group. APOE ɛ4 was associated with hippocampal volume loss only in the cognitively normal and MCI groups. APOE ɛ4 carriers with abnormal CSF Aβ in the MCI group acted synergistically to produce disproportionately greater volume loss than noncarriers. Conclusion Baseline CSF Aβ predicts progression of hippocampal volume loss. APOE ɛ4 carrier status amplifies the degree of neurodegeneration in MCI. Understanding the effect of interactions between genetic risk and amyloid pathology will be important in clinical trials and our understanding of the disease process.