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P1‐412: Effects of amyloid plaques and ApoE4 allele on brain connectivity in cognitively normal elderly
Author(s) -
Sheline Yvette,
Morris John,
Goate Allison,
Mintun Mark
Publication year - 2010
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.2010.05.967
Subject(s) - precuneus , default mode network , resting state fmri , pittsburgh compound b , neuropathology , apolipoprotein e , psychology , alzheimer's disease , voxel , neuroscience , disease , medicine , pathology , functional connectivity , functional magnetic resonance imaging , radiology
patients were presymptomatic with CDR-SOB of zero. Age and sex matched controls (n1⁄4 17) were recruited. Results: MAPT mutation carriers who were symptomatic were characterized by decreased N-acetylaspartate/creatine (NAA/Cr) ratio, an index of neuronal integrity, increased myoinositol (mI)/Cr ratio, a marker for glial activity, decreased NAA/mI and hippocampal atrophy (p 0.001). Whereas presymptomatic MAPT mutation carriers had elevated mI/Cr and decreased NAA/mI (p 0.001), NAA/Cr levels and hippocampal volumes were not different from controls. Decrease in NAA/ Cr (R 1⁄4 0. 33;p 1⁄4 0.016), NAA/mI (R 1⁄4 0.19;p 1⁄4 0.078), and hippocampal volumes (R1⁄4 0.56;p< 0.001) were associated with proximity to the expected or actual age of symptom onset in MAPT mutation carriers. Conclusions: The data suggest an ordered sequencing of the H MRS and MRI biomarkers. The neurodegenerative changes that are characterized by an elevation in the glial marker mI/Cr begin years before the onset of symptoms, and the decrease in the neuronal marker NAA/Cr and hippocampal atrophy appear to follow shortly before dementia ensues and become progressively more abnormal as dementia worsens. This sequence of H MRS and volumetric MRI changes in MAPT mutation carriers show similarities to the H MRS findings in sporadic and familial AD, and is in agreement with microglial activation observed prior to neuronal loss and hippocampal atrophy in tau transgenic mice. These early H MRS findings suggest that the mI/Cr ratio may be a useful inclusion biomarker for preventive trials in presymptomatic carriers of MAPT mutations and possibly other proteinopathies.