The large majority of Alzheimer's disease (AD) cases are sporadic with unknown genetic causes. In contrast, only a small percentage of AD cases are familial, with known genetic causes. Paradoxically, there are only few validated mouse models of sporadic AD but many of familial AD. Senescence Accelerated Mouse-Prone 8 (SAMP8) mice are a model of accelerated aging with features of sporadic AD. They exhibit a more complete suite of human AD-relevant pathologies than most familial models. SAMP8 brains are characterized by inflammation, glial activation, β-amyloid deposits, and hyperphosphorylated Tau. The excess amyloid deposits congregate around blood vessels leading to vascular impairment and leaky BBBs in these mice. SAMP8 mice also exhibit neuronal cell death, a feature not typically seen in models of familial AD. Additionally, adult hippocampal neurogenesis is decreased in SAMP8 mice and correspondingly, they have reduced cognitive ability. In line with this, hippocampal LTP is significantly compromised in SAMP8 mice. No model is perfect and SAMP8 mice are limited by the lack of clarity about their genomic differences from control SAMR1 (Senescence Accelerated Mouse-Resistant 1) mice although their transcriptomics changes are being revealed. To further complicate matters, multiple substrains of SAMP8 mice have emerged over the years, sometimes making comparisons of studies difficult. Despite these challenges, we argue that SAMP8 mice can be useful for studying AD-relevant symptoms and propose important experiments to strengthen this already useful model.
Keywords: Aging; Alzheimer’s; SAMP8; mouse models; neuroinflammation.
© The Author(s) 2025. Published by Oxford University Press.