Browsing by Author "Levey, Allan"

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    15 Years of Longitudinal Genetic, Clinical, Cognitive, Imaging, and Biochemical Measures in DIAN
    (medRxiv, 2024-08-09) Daniels, Alisha J.; McDade, Eric; Llibre-Guerra, Jorge J.; Xiong, Chengjie; Perrin, Richard J.; Ibanez, Laura; Supnet-Bell, Charlene; Cruchaga, Carlos; Goate, Alison; Renton, Alan E.; Benzinger, Tammie L. S.; Gordon, Brian A.; Hassenstab, Jason; Karch, Celeste; Popp, Brent; Levey, Allan; Morris, John; Buckles, Virginia; Allegri, Ricardo F.; Chrem, Patricio; Berman, Sarah B.; Chhatwal, Jasmeer P.; Farlow, Martin R.; Fox, Nick C.; Day, Gregory S.; Ikeuchi, Takeshi; Jucker, Mathias; Lee, Jae-Hong; Levin, Johannes; Lopera, Francisco; Takada, Leonel; Sosa, Ana Luisa; Martins, Ralph; Mori, Hiroshi; Noble, James M.; Salloway, Stephen; Huey, Edward; Rosa-Neto, Pedro; Sánchez-Valle, Raquel; Schofield, Peter R.; Roh, Jee Hoon; Bateman, Randall J.; Dominantly Inherited Alzheimer Network; Neurology, School of Medicine
    This manuscript describes and summarizes the Dominantly Inherited Alzheimer Network Observational Study (DIAN Obs), highlighting the wealth of longitudinal data, samples, and results from this human cohort study of brain aging and a rare monogenic form of Alzheimer's disease (AD). DIAN Obs is an international collaborative longitudinal study initiated in 2008 with support from the National Institute on Aging (NIA), designed to obtain comprehensive and uniform data on brain biology and function in individuals at risk for autosomal dominant AD (ADAD). ADAD gene mutations in the amyloid protein precursor (APP), presenilin 1 (PSEN1), or presenilin 2 (PSEN2) genes are deterministic causes of ADAD, with virtually full penetrance, and a predictable age at symptomatic onset. Data and specimens collected are derived from full clinical assessments, including neurologic and physical examinations, extensive cognitive batteries, structural and functional neuro-imaging, amyloid and tau pathological measures using positron emission tomography (PET), flurordeoxyglucose (FDG) PET, cerebrospinal fluid and blood collection (plasma, serum, and whole blood), extensive genetic and multi-omic analyses, and brain donation upon death. This comprehensive evaluation of the human nervous system is performed longitudinally in both mutation carriers and family non-carriers, providing one of the deepest and broadest evaluations of the human brain across decades and through AD progression. These extensive data sets and samples are available for researchers to address scientific questions on the human brain, aging, and AD.
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    Frontal Metabolites and Alzheimer’s Disease Biomarkers in Healthy Older Women and Women Diagnosed with Mild Cognitive Impairment
    (IOS Press, 2022) Hone-Blanchet, Antoine; Bohsali, Anastasia; Krishnamurthy, Lisa C.; Shahid, Salman S.; Lin, Qixiang; Zhao, Liping; Bisht, Aditya S.; John, Samantha E.; Loring, David; Goldstein, Felicia; Levey, Allan; Lah, James; Qiu, Deqiang; Crosson, Bruce; Radiology and Imaging Sciences, School of Medicine
    Background: Women account for two thirds of the prevalence and incidence of Alzheimer's disease (AD) and mild cognitive impairment (MCI). Evidence suggest that sex may differently influence the expression of proteins amyloid-beta (Aβ1-42) and tau, for which early detection is crucial in prevention of the disease. Objective: We investigated the effect of aging and cerebrospinal fluid (CSF) levels of Aβ1-42 and tau on frontal metabolites measured with proton magnetic resonance spectroscopy (MRS) in a cohort of cognitively normal older women and women with MCI. Methods: 3T single-voxel MRS was performed on the medial frontal cortex, using Point Resolved Spectroscopy (PRESS) and Mescher-Garwood Point Resolved Spectroscopy (MEGA-PRESS) in 120 women (age range 50-85). CSF samples of Aβ1-42 and tau and scores of general cognition were also obtained. Results: Levels of frontal gamma aminobutyric acid (GABA+) were predicted by age, independently of disease and CSF biomarkers. Importantly, levels of GABA+ were reduced in MCI patients. Additionally, we found that levels of N-acetylaspartate relative to myo-inositol (tNAA/mI) predicted cognition in MCI patients only and were not related to CSF biomarkers. Conclusion: This study is the first to demonstrate a strong association between frontal GABA+ levels and neurological aging in a sample consisting exclusively of healthy older women with various levels of CSF tau and Aβ1-42 and women with MCI. Importantly, our results show no correlation between CSF biomarkers and MRS metabolites in this sample.
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    Relationships between frontal metabolites and Alzheimer's disease biomarkers in cognitively normal older adults
    (Elsevier, 2022) Hone-Blanchet, Antoine; Bohsali, Anastasia; Krishnamurthy, Lisa C.; Shahid, Salman; Lin, Qixiang; Zhao, Liping; Loring, David; Goldstein, Felicia; John, Samantha E.; Fleischer, Candace C.; Levey, Allan; Lah, James; Qiu, Deqiang; Crosson, Bruce; Radiology and Imaging Sciences, School of Medicine
    Elevated expression of β-amyloid (Aβ1-42) and tau are considered risk-factors for Alzheimer's disease in healthy older adults. We investigated the effect of aging and cerebrospinal fluid levels of Aβ1-42 and tau on 1) frontal metabolites measured with proton magnetic resonance spectroscopy (MRS) and 2) cognition in cognitively normal older adults (n = 144; age range 50-85). Levels of frontal gamma aminobutyric acid (GABA+) and myo-inositol relative to creatine (mI/tCr) were predicted by age. Levels of GABA+ predicted cognitive performance better than mI/tCr. Additionally, we found that frontal levels of n-acetylaspartate relative to creatine (tNAA/tCr) were predicted by levels of t-tau. In cognitively normal older adults, levels of frontal GABA+ and mI/tCr are predicted by aging, with levels of GABA+ decreasing with age and the opposite for mI/tCr. These results suggest that age- and biomarker-related changes in brain metabolites are not only located in the posterior cortex as suggested by previous studies and further demonstrate that MRS is a viable tool in the study of aging and biomarkers associated with pathological aging and Alzheimer's disease.