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Association of deposition of tau and amyloid-? proteins with structural connectivity changes in cognitively normal older adults and Alzheimer's disease spectrum patients.

ABSTRACT: INTRODUCTION:Alzheimer's disease (AD) is characterized by accumulation of extracellular amyloid-? and intracellular tau neurofibrillary tangles. The recent advent of tau positron emission tomography (PET) has enabled in vivo assessment of tau pathology. The aim of this study was to explore whether tau deposition influences the structural connectivity in amyloid-negative and amyloid-positive groups, and further explore the difference between the groups. METHODS:We investigated 18 patients with amnestic mild cognitive impairment/mild AD (AD-spectrum group) and 35 cognitively normal older adults (CN group) using diffusion MRI, amyloid, and tau PET imaging. Diffusion connectometry was performed to identify white matter pathways correlated with each of the six variables of tau deposition in the bilateral hippocampi, temporal lobes, posterior and anterior cingulate cortices, precunei, orbitofrontal lobes, and entire cerebrum. RESULTS:The CN group showed increased connectivity along with an increased tau deposition in the bilateral hippocampi, temporal lobes, and entire cerebrum, whereas the AD-spectrum group showed decreased connectivity in the bilateral hippocampi, temporal lobes, anterior and posterior cingulate cortices, precunei, and entire cerebrum. CONCLUSION:These findings suggest that tau deposition in the CN group seems to induce a compensatory response against early neuronal injury or chronic inflammation associated with normal aging, whereas the coexistence of amyloid and tau in the AD-spectrum group seems to outweigh the compensatory response leading to decreased connectivity, suggesting that amyloid plays a crucial role in alternating structural connectivity.

SUBMITTER: Shigemoto Y

PROVIDER: S-EPMC6305935 | biostudies-other | 2018 Dec

REPOSITORIES: biostudies-other

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Association of deposition of tau and amyloid-β proteins with structural connectivity changes in cognitively normal older adults and Alzheimer's disease spectrum patients.

Shigemoto Yoko Y Sone Daichi D Maikusa Norihide N Okamura Nobuyuki N Furumoto Shozo S Kudo Yukitsuka Y Ogawa Masayo M Takano Harumasa H Yokoi Yuma Y Sakata Masuhiro M Tsukamoto Tadashi T Kato Koichi K Sato Noriko N Matsuda Hiroshi H

Brain and behavior 20181024 12

<h4>Introduction</h4>Alzheimer's disease (AD) is characterized by accumulation of extracellular amyloid-β and intracellular tau neurofibrillary tangles. The recent advent of tau positron emission tomography (PET) has enabled in vivo assessment of tau pathology. The aim of this study was to explore whether tau deposition influences the structural connectivity in amyloid-negative and amyloid-positive groups, and further explore the difference between the groups.<h4>Methods</h4>We investigated 18 p ...[more]

PMID: 30358161

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Project description:To improve the ability to develop treatments that prevent incipient Alzheimer disease (AD) from progressing to overt AD, it is important to understand the molecular basis of the earliest pathophysiological abnormalities and to determine how amyloid-? (A?) is involved very early in its pathogenesis.To investigate 2 specific A? oligomers, A? trimers and A?*56, in human cerebrospinal fluid (CSF); evaluate the effects of aging and AD; and obtain support for the hypothesis that they may be pathogenic by determining their relationships to CSF tau.A CSF sampling study.The University of Minnesota Medical School in Minneapolis, Minnesota, and the Salhgrenska University Hospital, Sweden.Forty-eight older adults with mild cognitive impairment or AD (impaired group); 49 age-matched cognitively intact control subjects (unimpaired group); and 10 younger, normal control subjects.Measurements of CSF A? trimers, A?*56, the 42-amino acid A? isoform (A?1-42), total tau (T-tau), and phospho-tau 181 (p-tau(181)). The hypothesis being tested was formulated after data collection. RESULTS We observed that A? trimers and A?*56 levels increased with age; within the unimpaired group, they were elevated in subjects with T-tau/A?1-42 ratios greater than a cutoff that distinguished the unimpaired group from subjects with AD. In the unimpaired group, T-tau and p-tau(181) were found to correlate strongly with A? trimers and A?*56 (r > 0.63), but not with A?1-42 (-0.10 < r < -0.01). The strong correlations were found to be attenuated in the impaired group.In cognitively intact older adults, CSF A? trimers and A?*56 were elevated in individuals at risk for AD, and they showed stronger relationships with tau than did A?1-42, a surrogate for A? fibril deposition. These findings suggest that prior to overt symptoms, 1 or both of the A? oligomers, but not fibrillar A?, is coupled to tau; however, this coupling is weakened or broken when AD advances to symptomatic stages. The uncoupling is interesting in light of the failure of experimental A? therapies to improve mild cognitive impairment/AD, which has prompted a shift in the timing of A? therapies to asymptomatic subjects. Knowing which A? species to target in asymptomatic subjects may enhance the success of future treatments for AD.

Dataset Information

Association of deposition of tau and amyloid-? proteins with structural connectivity changes in cognitively normal older adults and Alzheimer's disease spectrum patients.

Publications

Association of deposition of tau and amyloid-β proteins with structural connectivity changes in cognitively normal older adults and Alzheimer's disease spectrum patients.

Similar Datasets

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