Dataset Information

Microglial activation, but not tau pathology, is independently associated with amyloid positivity and memory impairment.

ABSTRACT: We sought to determine if upstream amyloid accumulation and downstream cognitive impairment have independent relationships with microglial activation and tau pathology. Fifty-eight older adults were stratified by amyloid and cognitive status based on ¹⁸F-florbetaben PET, history, and neuropsychological testing. Of these, 57 had ¹¹C-PBR28 PET to measure microglial activation and 43 had ¹⁸F-MK-6240 PET to measure tau pathology. Amyloid and cognitive status were associated with increased overall binding for both ¹¹C-PBR28 and ¹⁸F-MK-6240 (p's < 0.01). While there was no interaction between amyloid and cognitive status in their association with ¹¹C-PBR28 binding (p = 0.6722), there was an interaction in their association with ¹⁸F-MK-6240 binding (p = 0.0115). Binding of both radioligands was greater in amyloid-positive controls than in amyloid-negative controls; however, this difference was seen in neocortical regions for ¹¹C-PBR28 and only in medial temporal cortex for ¹⁸F-MK-6240. We conclude that, in the absence of cognitive symptoms, amyloid deposition has a greater association with microglial activation than with tau pathology.

SUBMITTER: Zou J

PROVIDER: S-EPMC6919274 | biostudies-literature | 2020 Jan

REPOSITORIES: biostudies-literature

ACCESS DATA

Publications

Microglial activation, but not tau pathology, is independently associated with amyloid positivity and memory impairment.

Zou James J Tao Sha S Johnson Aubrey A Tomljanovic Zeljko Z Polly Krista K Klein Julia J Razlighi Qolamreza R QR Brickman Adam M AM Lee Seonjoo S Stern Yaakov Y Kreisl William Charles WC

Neurobiology of aging 20190929

We sought to determine if upstream amyloid accumulation and downstream cognitive impairment have independent relationships with microglial activation and tau pathology. Fifty-eight older adults were stratified by amyloid and cognitive status based on 18F-florbetaben PET, history, and neuropsychological testing. Of these, 57 had 11C-PBR28 PET to measure microglial activation and 43 had 18F-MK-6240 PET to measure tau pathology. Amyloid and cognitive status were ass ...[more]

PMID: 31698286

Similar Datasets

Project description:Alzheimer's disease (AD) is associated with atrophy of the cornu ammonis (CA) 1 and the subiculum subfield of the hippocampus (HC), and with deficits in episodic memory and spatial orientation. These deficits are mainly associated with the functionality of the posterior HC. We therefore hypothesized that key AD pathologies, i.e., ?-amyloid and tau pathology would be particularly associated with the volume of the posterior subiculum in non-demented individuals. In our study we included 302 cognitively normal elderly participants (CN), 183 patients with subjective cognitive decline (SCD) and 171 patients with amnestic mild cognitive impairment (MCI), all of whom underwent 3T magnetic resonance images (MRI). The subicular subfield was segmented using Freesurfer 5.3 and divided into 10 volumetric segments moving from the most posterior (segment 1) to the most anterior part along the axis of the hippocampal head and body (segment 10). Cerebrospinal fluid (CSF) A?42 and phosphorylated tau (P-tau) were quantified using ELISA and were used as biomarkers for ?-amyloid and tau pathology, respectively. In the total sample, tau-pathology and A?-pathology and (measured by elevated P-tau and low A?42 levels in CSF) and mild memory dysfunction were mostly associated with the volume changes of the posterior subiculum. Both SCD and MCI patients with elevated P-tau or low A?42 levels displayed predominantly posterior subicular atrophy in comparisons to control subjects with normal CSF biomarker levels. Finally, there was no main effect of A?42 or P-tau when comparing SCD with abnormal P-tau or A?42 with SCD with normal levels of these CSF-biomarkers. However, in the left subiculum there was a significant interaction revealing atrophy in the left posterior but not the anterior subiculum in participants with low A?42 levels. The same pattern was observed on the contralateral side in participants with elevated P-tau levels. In conclusion, AD pathologies and mild memory dysfunction are mainly associated with atrophy of the posterior parts of the subicular subfields of the HC in non-demented individuals. In light of these findings we suggest that segmentation of the HC subfields may benefit from considering the volume of the different anterior-posterior subsections of each subfield.

Dataset Information

Microglial activation, but not tau pathology, is independently associated with amyloid positivity and memory impairment.

Publications

Microglial activation, but not tau pathology, is independently associated with amyloid positivity and memory impairment.

Similar Datasets

OmicsDI is part of the ELIXIR infrastructure

Tweets