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.
Highlights
Alzheimer’s Disease (AD) is a worldwide plague affecting millions of people in aging societies
local field potential (LFP) recordings were obtained with a multi-site linear probe sampling from the posterior parietal cortex (PPC), through the hippocampal formation (HPF) up to the dentate gyrus (DG) as previously described [42] and summarized in Supplementary Materials
Compared to 3-month-old WT mice, young AD mice show a significant reduction in total power, especially at the hippocampal level, being halved in CA1 at the stratum radiatum-lacunosum molecolare, a reduction that is maintained in middleaged AD mice (Figure 1C)
Summary
Alzheimer’s Disease (AD) is a worldwide plague affecting millions of people in aging societies. It has huge social and economic costs, considering the lack of effective therapies; its prevalence is expected to increase, especially in low- and middle-income countries, with an estimated 139 million affected individuals by 2050 Very little is known about the processes that cause conversion from healthy aging to mild cognitive impairment (MCI) and, from this condition, to AD, even if improvements in electroencephalographic (EEG) recordings potentially allow to follow MCI to AD conversion [2,3]. There is an urgent need for biomarkers that allow identification of AD staging and even more for markers associated with a high probability of disease worsening [4,5]
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