Cerebrospinal Fluid Biomarkers are Differentially Related to Structural and Functional Changes in Dementia of the Alzheimer’s Type

Abstract

The two cardinal pathologies of Alzheimer's disease (AD) develop according to distinct anatomical trajectories. Cerebral tau-related pathology first accumulates in the mesial temporal region, while amyloid-related pathology first appears in neocortex. The eventual distributions of these pathologies reflect their anatomical origins. An implication is that the cardinal pathologies might exert preferential effects on the structurofunctional brain changes observed in AD. We investigated this hypothesis in 39 patients with dementia of the Alzheimer's type. Interrelationships were analyzed between cerebrospinal fluid biomarkers of the cardinal pathologies, volumetric brain changes using magnetic resonance imaging, and brain metabolism using [18F]-FDG-PET. Amyloid-related pathology was preferentially associated with structurofunctional changes in the precuneus and lateral temporal regions. Tau-related pathology was not associated with changes in these regions. These findings support the hypothesis that tau- and amyloid-pathology exert differential effects on structurofunctional changes in the AD brain. These findings have implications for future therapeutic trials and hint at a more complex relationship between the cardinal pathologies and disruption of brain networks.

Coupling relationship between glucose and oxygen metabolisms to differentiate preclinical Alzheimer's disease and normal individuals

“…The DMN is the most vulnerable network to amyloid deposition (Buckner et al, 2005; Shin et al, 2010; Sperling et al, 2009), showing abnormalities in multiple modalities (Grothe & Teipel, 2016). Precuneus and posterior cingulate cortex, as the key nodes in the DMN, also are highly vulnerable to various pathological changes (Gordon et al, 2018; Malpas et al, 2018), which was further confirmed in this study. Compared with the entire brain level, in the brain region of the DMN, the metabolism, spontaneous activity, and energy–oxygen coupling are related to the global Aβ deposition.…”

“…In this study, we examined 62 right-handed and Mandarin-speaking subjects with ages ranging 50-79 years, comprising 27 NC subjects, 20 preADs, and 15 CI patients. The data were obtained from the Sino Longitudinal Study on Cognitive Decline (SILCODE) project (Li, Wang, Su, Hu, & Han, 2019) (ClinicalTrials.gov Identifier #NCT03370744).…”

Dissociation of energy connectivity and functional connectivity in Alzheimer's disease is associated with maintenance of cognitive performance

“…The DMN module is the network most susceptible to amyloid accumulation [ 27 ]. Therefore, a common hypothesis is that the DMN network module region is the preferred target for ad-related pathological processes, including Aβdeposition [ 27 ].…”

“…The DMN module is the network most susceptible to amyloid accumulation [ 27 ]. Therefore, a common hypothesis is that the DMN network module region is the preferred target for ad-related pathological processes, including Aβdeposition [ 27 ]. The correlation between FDG-SUVR and ReHo values in the DMN network gradually decreases with the increasing accumulation of amyloid [ 13 ].…”