Plasma Tau Association with Brain Atrophy in Mild Cognitive Impairment and Alzheimer’s Disease

Abstract

Abstract.Background: Peripheral (plasma) and central (cerebrospinal fluid, CSF) measures of tau are higher in Alzheimer's disease (AD) relative to prodromal stages and controls. While elevated CSF tau concentrations have been shown to be associated with lower grey matter density (GMD) in AD-specific regions, this correlation has yet to be examined for plasma in a large study. Objective: Determine the neuroanatomical correlates of plasma tau using voxel-based analysis. Methods: Cross-sectional data for 508 ADNI participants were collected for clinical, plasma total-tau (t-tau), CSF amyloid (A␤ 42 ) and tau, and MRI variables. The relationship between plasma tau and GMD and between CSF t-tau and GMD were assessed on a voxel-by-voxel basis using regression models. Age, sex, APOE ε4 status, diagnosis, and total intracranial volume were used as covariates where appropriate. Participants were defined as amyloid positive (A␤+) if CSF A␤ 42 was <192 pg/mL. Results: Plasma tau was negatively correlated with GMD in the medial temporal lobe (MTL), precuneus, thalamus, and striatum. The associations with thalamus and striatum were independent of diagnosis. A negative correlation also existed 1 Data used in preparation of this article were obtained from the Alzheimer's Disease Neuroimaging Initiative (ADNI) database (http://adni.loni.usc.edu). As such, the investigators within the ADNI contributed to the design and implementation of ADNI and/or provided data but did not participate in analysis or writing of this report. A complete listing of ADNI investigators can be found at: http://adni.loni.usc.edu/ wp-content/uploads/how to apply/ADNI Acknowledgement List. pdf. K.D. Deters et al. / Plasma Tau is Associated with Brain Atrophybetween plasma tau and GMD in A␤+ participants in the MTL, precuneus, and frontal lobe. When compared to CSF t-tau, plasma tau showed a notably different associated brain atrophy pattern, with only small overlapping regions in the fusiform gyrus. Conclusion: Plasma tau may serve as a non-specific marker for neurodegeneration but is still relevant to AD considering low GMD was associated with plasma tau in A␤+ participants and not A␤-participants.

Plasma Amyloid as Prescreener for the Earliest Alzheimer Pathological Changes

“…Moreover, plasma tTau levels were correlated with neither CSF tTau nor CSF pTau181 levels. Former studies have shown diagnostic value of plasma tTau, but only at the stage of full‐blown dementia 35, 36, 37, 38, 39. Thus far, no studies have focused on nondemented individuals only.…”

Interactive Effects of Racial Identity and Repetitive Head Impacts on Cognitive Function, Structural MRI-Derived Volumetric Measures, and Cerebrospinal Fluid Tau and Aβ

“…After aspiration, approximately 10 ml of CSF was deposited into a polypropylene transfer tube and frozen at -80 • C. Aliquots were shipped to the University of Pennsylvania for batch analysis of t-tau, p-tau 181 , and Aβ 1−42 . Methods of CSF biomarker analysis of t-tau, p-tau 181 , and Aβ 1−42 are described elsewhere (Shaw et al, 2009;Grossman et al, 2014;Deters et al, 2017;Alosco et al, 2018c). Concentrations of these analytes served as outcomes for markers of neurodegeneration (t-tau), hyperphosphorylated tau (p-tau 181 ), and amyloidosis (Aβ 1−42 ).…”

Deep learning detection of informative features in tau PET for Alzheimer’s disease classification

“…The amount and spatial distribution of abnormal tau, seen pathologically as neurofibrillary tangles in brain, is closely related to the onset of cognitive decline and the progression of AD. The identification of morphological phenotypes of tau on in vivo neuroimaging may help to differentiate mild cognitive impairment (MCI) and AD from cognitively normal older adults (CN) and provide insights regarding disease mechanisms and patterns of progression [6][7][8][9].…”