Late-Life Obesity Associated with Tau Pathology in Cognitively Normal Individuals: The CABLE Study

2021 ◽  
pp. 1-11
Author(s):  
Xiao-Xue Zhang ◽  
Ya-Hui Ma ◽  
He-Ying Hu ◽  
Ling-Zhi Ma ◽  
Lan Tan ◽  
...  
Keyword(s):  
Central Obesity ◽  
Amyloid Β ◽  
Late Life ◽  
Inverse Association ◽  
Life Stages ◽  
Tau Pathology ◽  
Cognitively Normal ◽  
Normal Individuals ◽  
Obesity Indices ◽  
T Tau

Background: Existed evidence suggests that midlife obesity increases the risk of Alzheimer’s disease (AD), while there is an inverse association between AD and obesity in late life. However, the underlying metabolic changes of AD pathological proteins attributed to obesity in two life stages were not clear. Objective: To investigate the associations of obesity types and obesity indices with AD biomarkers in cerebrospinal fluid (CSF) in different life stages. Methods: We recruited 1,051 cognitively normal individuals (61.94±10.29 years, 59.66%male) from the Chinese Alzheimer’s Biomarker and LifestylE (CABLE) study with CSF detections for amyloid-β 42 (Aβ 42), total-tau (T-tau), and phosphorylated tau (P-tau). We utilized body mass index, waist circumference, waist-to-height ratio, and metabolic risk factors to determine human obesity types. Multiple linear models and interaction analyses were run to assess the impacts of obesity on AD biomarkers. Results: The metabolically unhealthy obesity or healthy obesity might exert a reduced tau pathology burden (p <  0.05). Individuals with overweight, general obesity, and central obesity presented lower levels of tau-related proteins in CSF than normal controls (p <  0.05). Specially, for late-life individuals, higher levels of obesity indices were associated with a lower load of tau pathology as measured by CSF T-tau and T-tau/Aβ 42 (p <  0.05). No similar significant associations were observed in midlife. Conclusion: Collectively, late-life general and central obesity seems to be associated with the reduced load of tau pathology, which further consolidates the favorable influence of obesity in specific life courses for AD prevention.

scholarly journals Higher Body Mass Index Is Associated with Lower Cortical Amyloid-β Burden in Cognitively Normal Individuals in Late-Life

2019 ◽  
Vol 69 (3) ◽  
pp. 817-827 ◽  
Author(s):  
Vineeth Thirunavu ◽  
Austin McCullough ◽  
Yi Su ◽  
Shaney Flores ◽  
Aylin Dincer ◽  
...  
Keyword(s):  
Body Mass Index ◽  
Body Mass ◽  
Amyloid Β ◽  
Late Life ◽  
Cognitively Normal ◽  
Normal Individuals

scholarly journals Increased midlife triglycerides predict brain β-amyloid and tau pathology 20 years later

Neurology ◽  
2017 ◽  
Vol 90 (1) ◽  
pp. e73-e81 ◽  
Author(s):  
Katarina Nägga ◽  
Anna-Märta Gustavsson ◽  
Erik Stomrud ◽  
Daniel Lindqvist ◽  
Danielle van Westen ◽  
...  
Keyword(s):  
Risk Factors ◽  
Low Density Lipoprotein ◽  
Density Lipoprotein ◽  
Healthy Population ◽  
Lipid Levels ◽  
Tau Pathology ◽  
Lipoprotein Subfractions ◽  
Cognitively Normal ◽  
Normal Individuals ◽  
Β Amyloid

ObjectiveTo evaluate the effect of midlife lipid levels on Alzheimer brain pathology 20 years later in cognitively normal elderly individuals.MethodsThis is a longitudinal cohort study of 318 cognitively normal individuals with data on fasting lipid levels at midlife (mean age 54 years). Presence of β-amyloid (Aβ) and tau pathologies 20 years later (mean age 73 years) were detected by quantifying Alzheimer disease (AD) biomarkers in CSF. In a subset (n = 134), Aβ (18F-flutemetamol) PET was also performed.ResultsCSF Aβ42 and Aβ PET revealed Aβ pathology in approximately 20% of the cognitively healthy population and CSF Aβ42/phosphorylated tau (p-tau) ratio indicated both Aβ and tau pathology in 16%. Higher levels of triglycerides in midlife were independently associated with abnormal CSF Aβ42 (odds ratio [OR] 1.34, 95% confidence interval [CI] 1.03–1.75, p = 0.029) and abnormal Aβ42/p-tau ratio (OR 1.46, 95% CI 1.10–1.93; p = 0.009) adjusting for age, sex, APOE ε4, education, and multiple vascular risk factors. Triglycerides were also associated with abnormal Aβ PET in multivariable regression models, but the association was attenuated in the fully adjusted model. Increased levels of medium and large low-density lipoprotein subfractions were significantly associated with abnormal Aβ PET and large high-density lipoprotein particles were associated with decreased risk of abnormal Aβ PET.ConclusionsIncreased levels of triglycerides at midlife predict brain Aβ and tau pathology 20 years later in cognitively healthy individuals. Certain lipoprotein subfractions may also be risk factors for Aβ pathology. These findings further support an involvement of lipids in the very early stages of AD development.

scholarly journals Plasma amyloid β 40/42 ratio predicts cerebral amyloidosis in cognitively normal individuals at risk for Alzheimer's disease

2019 ◽  
Vol 15 (6) ◽  
pp. 764-775 ◽  
Author(s):  
Andrea Vergallo ◽  
Lucile Mégret ◽  
Simone Lista ◽  
Enrica Cavedo ◽  
Henrik Zetterberg ◽  
...  
Keyword(s):  
Alzheimer’S Disease ◽  
Alzheimer's Disease ◽  
At Risk ◽  
Amyloid Β ◽  
Cognitively Normal ◽  
Cerebral Amyloidosis ◽  
Normal Individuals

scholarly journals Association of amyloid-β CSF/PET discordance and tau load 5 years later

Neurology ◽  
2020 ◽  
Vol 95 (19) ◽  
pp. e2648-e2657 ◽  
Author(s):  
Juhan Reimand ◽  
Lyduine Collij ◽  
Philip Scheltens ◽  
Femke Bouwman ◽  
Rik Ossenkoppele ◽  
...  
Keyword(s):  
Cognitive Impairment ◽  
Mild Cognitive Impairment ◽  
Amyloid Β ◽  
Csf Biomarkers ◽  
Tau Pathology ◽  
Cognitively Normal ◽  
Amyloid Aβ ◽  
Β Amyloid ◽  
Tau Pet

ObjectiveTo investigate the association between discordant β-amyloid (Aβ) PET and CSF biomarkers at baseline and the emergence of tau pathology 5 years later.MethodsWe included 730 Alzheimer's Disease Neuroimaging Initiative (ADNI) participants without dementia (282 cognitively normal, 448 mild cognitive impairment) with baseline [18F]florbetapir PET and CSF Aβ42 available. Aβ CSF/PET status was determined at baseline using established cutoffs. Longitudinal data were available for [18F]florbetapir (Aβ) PET (baseline to 4.3 ± 1.9 years), CSF (p)tau (baseline to 2.0 ± 0.1 years), cognition (baseline to 4.3 ± 2.0 years), and [18F]flortaucipir (tau) PET (measured 5.2 ± 1.2 years after baseline to 1.6 ± 0.7 years later). We used linear mixed modeling to study the association between Aβ CSF/PET status and tau pathology measured in CSF or using PET. We calculated the proportion of CSF+/PET− participants who during follow-up (1) progressed to Aβ CSF+/PET+ or (2) became tau-positive based on [18F]flortaucipir PET.ResultsAβ CSF+/PET+ (n = 318) participants had elevated CSF (p)tau levels and worse cognitive performance at baseline, while CSF+/PET− (n = 80) participants were overall similar to the CSF−/PET− (N = 306) group. Five years after baseline, [18F]flortaucipir PET uptake in the CSF+/PET− group (1.20 ± 0.13) did not differ from CSF−/PET− (1.18 ± 0.08, p = 0.69), but was substantially lower than CSF+/PET+ (1.48 ± 0.44, p < 0.001). Of the CSF+/PET− participants, 21/64 (33%) progressed to Aβ CSF+/PET+, whereas only one (3%, difference p < 0.05) became tau-positive based on [18F]flortaucipir PET.ConclusionsAβ load detectable by both CSF and PET seems to precede substantial tau deposition. Compared to participants with abnormal Aβ levels on both PET and CSF, the CSF+/PET− group has a distinctly better prognosis.

scholarly journals Plasma amyloid β 42/40 ratios as biomarkers for amyloid β cerebral deposition in cognitively normal individuals

2017 ◽  
Vol 8 (1) ◽  
pp. 179-187 ◽  
Author(s):  
Noelia Fandos ◽  
Virginia Pérez‐Grijalba ◽  
Pedro Pesini ◽  
Salvador Olmos ◽  
Matías Bossa ◽  
...  
Keyword(s):  
Amyloid Β ◽  
Cognitively Normal ◽  
Normal Individuals

Mesial temporal tau is related to worse cognitive performance and greater neocortical tau load in amyloid-β–negative cognitively normal individuals

2021 ◽  
Vol 97 ◽  
pp. 41-48
Author(s):  
Colin Groot ◽  
Vincent Doré ◽  
Joanne Robertson ◽  
Samantha C. Burnham ◽  
Greg Savage ◽  
...  
Keyword(s):  
Cognitive Performance ◽  
Amyloid Β ◽  
Cognitively Normal ◽  
Normal Individuals

O4-03-03: Increased Amyloid-β-related Hypometabolism in Cognitively Normal Individuals with Late-onset Alzheimer's Affected Parents

2010 ◽  
Vol 6 ◽  
pp. e15-e16
Author(s):  
Lisa Mosconi ◽  
Juha Rinne ◽  
Wai Tsui ◽  
Yi Li ◽  
John Murray ◽  
...  
Keyword(s):  
Late Onset ◽  
Amyloid Β ◽  
Cognitively Normal ◽  
Normal Individuals

scholarly journals Olfactory Impairment is Related to Tau Pathology and Neuroinflammation in Alzheimer’s Disease

2021 ◽  
pp. 1-16
Author(s):  
Julia Klein ◽  
Xinyu Yan ◽  
Aubrey Johnson ◽  
Zeljko Tomljanovic ◽  
James Zou ◽  
...  
Keyword(s):  
Alzheimer’S Disease ◽  
Alzheimer's Disease ◽  
Brain Mri ◽  
Amyloid Β ◽  
Cognitive Status ◽  
Odor Identification ◽  
Amyloid Pet ◽  
Tau Pathology ◽  
Olfactory Impairment ◽  
T Tau

Background: Olfactory impairment is evident in Alzheimer’s disease (AD); however, its precise relationships with clinical biomarker measures of tau pathology and neuroinflammation are not well understood. Objective: To determine if odor identification performance measured with the University of Pennsylvania Smell Identification Test (UPSIT) is related to in vivo measures of tau pathology and neuroinflammation. Methods: Cognitively normal and cognitively impaired participants were selected from an established research cohort of adults aged 50 and older who underwent neuropsychological testing, brain MRI, and amyloid PET. Fifty-four participants were administered the UPSIT. Forty-one underwent 18F-MK-6240 PET (measuring tau pathology) and fifty-three underwent 11C-PBR28 PET (measuring TSPO, present in activated microglia). Twenty-three participants had lumbar puncture to measure CSF concentrations of total tau (t-tau), phosphorylated tau (p-tau), and amyloid-β (Aβ 42). Results: Low UPSIT performance was associated with greater18F-MK-6240 binding in medial temporal cortex, hippocampus, middle/inferior temporal gyri, inferior parietal cortex, and posterior cingulate cortex (p <  0.05). Similar relationships were seen for 11C-PBR28. These relationships were primarily driven by amyloid-positive participants. Lower UPSIT performance was associated with greater CSF concentrations of t-tau and p-tau (p <  0.05). Amyloid status and cognitive status exhibited independent effects on UPSIT performance (p <  0.01). Conclusion: Olfactory identification deficits are related to extent of tau pathology and neuroinflammation, particularly in those with amyloid pathophysiology. The independent association of amyloid-positivity and cognitive impairment with odor identification suggests that low UPSIT performance may be a marker for AD pathophysiology in cognitive normal individuals, although impaired odor identification is associated with both AD and non-AD related neurodegeneration. NCT Registration Numbers: NCT03373604; NCT02831283

scholarly journals Medial Temporal Tau Pathology Is Associated With Verbal Memory

2020 ◽  
Vol 4 (Supplement_1) ◽  
pp. 767-767
Author(s):  
Murat Bilgel ◽  
Jacob Ziontz ◽  
Andrea Shafer ◽  
Luigi Ferrucci ◽  
Dean Wong ◽  
...  
Keyword(s):  
Entorhinal Cortex ◽  
Verbal Memory ◽  
Memory Performance ◽  
Cognitive Status ◽  
Therapeutic Interventions ◽  
Tau Pathology ◽  
Cognitively Normal ◽  
Positron Emission ◽  
Normal Individuals ◽  
Baltimore Longitudinal Study

Abstract Medial temporal tau pathology is frequently observed in individuals over 70 regardless of cognitive status. To understand the link between tau and cognitive performance, we evaluated tau pathology using 18F-flortaucipir positron emission tomography among 95 cognitively normal participants from the Baltimore Longitudinal Study of Aging. We examined tau levels in early Braak regions (entorhinal cortex and hippocampus) in relation to verbal episodic memory performance concurrent with and prior to the tau scan using linear mixed effects models adjusted for age, sex, amyloid status, and time from PET scan. Higher hippocampal tau burden had a trend-level association with lower concurrent memory performance (p=0.05). Greater tau pathology in the hippocampus and entorhinal cortex was associated with steeper decline in memory performance prior to tau scan (p=0.013 and 0.026, respectively). These findings suggest that therapeutic interventions targeting tau pathology may need to be administered early among cognitively normal individuals to prevent memory decline.

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