Neuroimaging biomarkers of glial activation for predicting the annual cognitive function decline in patients with Alzheimer's disease

Fumihiko Yasuno; Yasuyuki Kimura; Aya Ogata; Hiroshi Ikenuma; Junichiro Abe; Hiroyuki Minami; Takashi Nihashi; Kastunori Yokoi; Saori Hattori; Nobuyoshi Shimoda; Atsushi Watanabe; Kensaku Kasuga; Takeshi Ikeuchi; Akinori Takeda; Takashi Sakurai; Kengo Ito; Takashi Kato

doi:10.1016/j.bbi.2023.08.027

Neuroimaging biomarkers of glial activation for predicting the annual cognitive function decline in patients with Alzheimer's disease

Brain Behav Immun. 2023 Nov:114:214-220. doi: 10.1016/j.bbi.2023.08.027. Epub 2023 Aug 28.

Authors

Fumihiko Yasuno¹, Yasuyuki Kimura², Aya Ogata³, Hiroshi Ikenuma⁴, Junichiro Abe⁴, Hiroyuki Minami⁵, Takashi Nihashi⁵, Kastunori Yokoi⁵, Saori Hattori⁴, Nobuyoshi Shimoda⁶, Atsushi Watanabe⁷, Kensaku Kasuga⁸, Takeshi Ikeuchi⁸, Akinori Takeda⁵, Takashi Sakurai⁵, Kengo Ito², Takashi Kato²

Affiliations

¹ National Hospital for Geriatric Medicine, National Center for Geriatrics and Gerontology, Obu, Japan; Department of Clinical and Experimental Neuroimaging, Center for Development of Advanced Medicine for Dementia, National Center for Geriatrics and Gerontology, Obu, Japan. Electronic address: yasunof@ncgg.go.jp.
² National Hospital for Geriatric Medicine, National Center for Geriatrics and Gerontology, Obu, Japan; Department of Clinical and Experimental Neuroimaging, Center for Development of Advanced Medicine for Dementia, National Center for Geriatrics and Gerontology, Obu, Japan.
³ Department of Clinical and Experimental Neuroimaging, Center for Development of Advanced Medicine for Dementia, National Center for Geriatrics and Gerontology, Obu, Japan; Department of Pharmacy, Faculty of Pharmacy, Gifu University of Medical Science, Kani, Japan.
⁴ Department of Clinical and Experimental Neuroimaging, Center for Development of Advanced Medicine for Dementia, National Center for Geriatrics and Gerontology, Obu, Japan.
⁵ National Hospital for Geriatric Medicine, National Center for Geriatrics and Gerontology, Obu, Japan.
⁶ Molecular Analysis Division, Center for Core Facility Administration, National Center for Geriatrics and Gerontology, Obu, Japan.
⁷ Equipment Management Division, Center for Core Facility Administration, National Center for Geriatrics and Gerontology, Obu, Japan.
⁸ Department of Molecular Genetics, Brain Research Institute, Niigata University, Niigata, Japan.

PMID: 37648003
DOI: 10.1016/j.bbi.2023.08.027

Abstract

Background: Glial activation is central to the pathogenesis of Alzheimer's disease (AD). However, researchers have not demonstrated its relationship to longitudinal cognitive deterioration. We aimed to compare the prognostic effects of baseline positron emission tomography (PET) imaging of glial activation and amyloid/tau pathology on the successive annual cognitive decline in patients with AD.

Methods: We selected 17 patients diagnosed with mild cognitive impairment or AD. We assessed the annual changes in global cognition and memory. Furthermore, we assessed the predictive effects of baseline amyloid and tau pathology indicated by cerebrospinal fluid (CSF) concentrations and PET imaging of glial activation (¹¹C-DPA-713-binding potential in the area of Braak 1-3 [¹¹C-DPA-713-BP_ND]) on global cognition and memory using a stepwise regression analysis.

Results: The final multiple regression model of annual changes in global cognition and memory scores included ¹¹C-DPA-713-BP_ND as the predictor. The CSF Aβ42/40 ratios and p-tau concentrations were removed from the final model. In stepwise Bayesian regression analysis, the Bayes factor-based model comparison suggested that the best model included ¹¹C-DPA-713-BP_ND as the predictor of decline in global cognition and memory.

Conclusions: Translocator protein-PET imaging of glial activation is a stronger predictor of AD clinical progression than the amount of amyloid/tau pathology measured using CSF concentrations. Glial activation is the primary cause of tau-induced neuronal toxicity and cognitive deterioration, thereby highlighting the potential of blocking maladaptive microglial responses as a therapeutic strategy for AD treatment.

Keywords: Alzheimer’s disease; Cognitive decline; Glial activation; Neuroinflammation; Positron emission tomography; Tau pathology.

Publication types

Research Support, Non-U.S. Gov't

MeSH terms

Alzheimer Disease* / pathology
Amyloid beta-Peptides / cerebrospinal fluid
Bayes Theorem
Biomarkers / cerebrospinal fluid
Cognition / physiology
Cognitive Dysfunction* / diagnostic imaging
Cognitive Dysfunction* / pathology
Humans
Neuroimaging
Positron-Emission Tomography / methods
tau Proteins / cerebrospinal fluid

Substances

N,N-diethyl-2-(2-(4-methoxyphenyl)-5,7-dimethyl-pyrazolo(1,5-a)pyrimidin-3-yl)-acetamide
tau Proteins
Biomarkers
Amyloid beta-Peptides