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Alzheimer's disease (AD) is the most prevalent form of dementia, but no effective therapeutic strategy is available to date. Rhythmic magnetic stimulation is an attractive means of neuron modulation that could be beneficial for restoring learning and memory abilities. To assess the effect of a compound pulsed rhythmic magnetic field (cPMF) on cognition during AD progression and to explore the appropriate cPMF intervention period. Female 5xFAD mice aged 10 weeks and 18 weeks were exposed to cPMF with a carrier frequency of 40 Hz, repeated at 5 Hz for 1 h/d for 8 consecutive weeks. The Morris water maze (MWM) test was used for cognitive behavioral assessment. Furthermore, changes in molecular pathology within the brain were detected using immunofluorescence staining and real-time PCR. 10-week-old AD mice treated with cPMF explored the target quadrant more frequently than sham-exposed AD mice in MWM test, exhibiting improved learning and memory abilities. Additionally, cPMF exposure alleviated Aβ plaque deposition and astrogliosis in the AD brain. Moreover, neurotrophic factor fibroblast growth factor 1 (FGF1) in the AD brain was upregulated by cPMF treatment. However, in 18-week-old AD mice treated with cPMF, cognitive performance and Fgf1 gene expression were not significantly improved, although Aβ plaque deposition and astrogliosis were alleviated. Early intervention via long-term rhythmic cPMF stimulation may alleviate the histopathological features and enhance neuroprotective gene Fgf1 expression, thereby improving the cognitive performance of 5xFAD mice, which should provide promising insight for the clinical treatment of patients with AD. • Magnetic stimulation with θ rhythm-modulated γ frequency could enhance the learning and memory abilities of 5xFAD mice. • Early rather than late intervention via the cPMF could improve the cognitive behavioral performance of AD mice. • Both early and late cPMF treatments could alleviate Aβ plaque deposition and astrogliosis of AD mice. • Effectiveness of early cPMF intervention might be attributed to the enhanced expression level of neuroprotective Fgf1 gene. [ABSTRACT FROM AUTHOR]

Traumatic brain injury (TBI) is a risk factor for the development of Alzheimer''s disease (AD). This immunohistochemical study determined the extent of AD-related changes in temporal cortex resected from individuals treated surgically for severe TBI. Antisera generated against Aβ species (total Aβ, Aβ1–42, and Aβ1–40), the C-terminal of the Aβ precursor protein (APP), apolipoprotein E (apoE), and markers of neuron structure and degeneration (tau, ubiquitin, α-, β-, and γ-synuclein) were used to examine the extent of Aβ plaque deposition and neurodegenerative changes in 18 TBI subjects (ages 18–64 years). Diffuse cortical Aβ deposits were observed in one third of subjects (aged 35–62 years) as early as 2 h after injury, with only one (35-year old) individual exhibiting “mature”, dense-cored plaques. Plaque-like deposits, neurons, glia, and axonal changes were also immunostained with APP and apoE antibodies. In plaque-positive cases, the only statistically significant change in cellular immunostaining was increased neuronal APP (P = 0.013). There was no significant correlation between the distribution of Aβ plaques and markers of neuronal degeneration. Diffuse tau immunostaining was localized to neuronal cell soma, axons or glial cells in a larger subset of individuals. Tau-positive, neurofibrillary tangle (NFT)-like changes were detected in only two subjects, both of more advanced age and who were without Aβ deposits. Other neurodegenerative changes, evidenced by ubiquitin- and synuclein-immunoreactive neurons, were abundant in the majority of cases. Our results demonstrate a differential distribution and course of intra- and extra-cellular AD-like changes during the acute phase following severe TBI in humans. Aβ plaques and early evidence of neuronal degenerative changes can develop rapidly after TBI, while fully developed NFTs most likely result from more chronic disease- or injury-related processes. These observations lend further support to the hypothesis that head trauma significantly increases the risk of developing pathological and clinical symptoms of AD, and provide insight into the molecular mechanisms that initiate these pathological cascades very early during severe brain injury. [Copyright &y& Elsevier]