Accelerated Aging Characterizes the Early Stage of Alzheimer’s Disease

Abstract

For Alzheimer’s disease (AD), aging is the main risk factor, but whether cognitive impairments due to aging resemble early AD deficits is not yet defined. When working with mouse models of AD, the situation is just as complicated, because only a few studies track the progression of the disease at different ages, and most ignore how the aging process affects control mice. In this work, we addressed this problem by comparing the aging process of PS2APP (AD) and wild-type (WT) mice at the level of spontaneous brain electrical activity under anesthesia. Using local field potential recordings, obtained with a linear probe that traverses the posterior parietal cortex and the entire hippocampus, we analyzed how multiple electrical parameters are modified by aging in AD and WT mice. With this approach, we highlighted AD specific features that appear in young AD mice prior to plaque deposition or that are delayed at 12 and 16 months of age. Furthermore, we identified aging characteristics present in WT mice but also occurring prematurely in young AD mice. In short, we found that reduction in the relative power of slow oscillations (SO) and Low/High power imbalance are linked to an AD phenotype at its onset. The loss of SO connectivity and cortico-hippocampal coupling between SO and higher frequencies as well as the increase in UP-state and burst durations are found in young AD and old WT mice. We show evidence that the aging process is accelerated by the mutant PS2 itself and discuss such changes in relation to amyloidosis and gliosis.

Patterns of Aging Changes in Bodyweight May Predict Alzheimer’s Disease

“…Respectively, younger age at reaching maximum weight, and faster decline in weight towards older ages were associated with higher AD risk. This points to a major role of accelerated physical aging in AD, which was also suggested by others [ 18 ]. A more detailed analysis of the interaction between AgeMax and weight groups (that is, whether the association between AgeMax and AD risk varies in normal weight and overweight/obese groups) would also be helpful in future studies.…”

The role of ADAM10 in astrocytes: Implications for Alzheimer’s disease

“…Interestingly, wild-type mice showed a trajectory toward high GFAP cluster astrocytes with aging (Habib et al, 2020). In support of this, increased GFAP reactivity was shown to be present in both aged mice and in the earlier development of double transgenic (B6.152H) mouse line, suggesting FAD mutations may represent an accelerated aging phenotype (Leparulo et al, 2022). In humans elevated GFAP has been identified in both cognitively healthy aging and AD, reflecting cognitive ability irrespective of diagnosis (Bettcher et al, 2021).…”

Cross-layer Balance of Visuo-hippocampal Functional Connectivity Is Associated With Episodic Memory Recognition Accuracy

“…The discovered behavioral correlation with the cross-layer imbalance of cortico-hippocampal FC could have great impact outside of healthy young adults, particularly for examining biomarkers of neurodegenerative diseases. As deep/super cial cortical layers were associated with low/high-frequency oscillations, the high/low frequency power imbalance has been shown to be associated with early Alzheimer's disease 56 . The alterations in hippocampal theta-gamma coupling were found to start earlier than plaque deposition 57 .…”