Casualties of context? Risk of cognitive, behavioral and physical health difficulties among children living in high-incarceration neighborhoods.

Alzheimer's disease (AD) is defined by two pathologies—amyloid beta (Aβ) plaques and neurofibrillary tangles. However, less emphasis is placed on the heterogeneity of processes in AD, which impedes us from determining novel potential mechanistic pathways preceding clinical symptoms and identifying effective markers for treatment. Although Aβ is hypothesized to initiate a biological cascade that leads to accelerated deposition and spread of tau pathology and neurodegeneration, there are likely multiple pathways that converge to promote neurodegeneration and cognitive impairment. Studying different and multiple neuroinflammatory pathways that reduce AD and vascular pathology is an important precursor to the development of single and multi‐targeted therapies. One such pathway involves the interplay between neuroinflammation and cerebrovascular burden, which may parallel the cascading impact of Aβ pathology. Reactive astrocytes and microglia are important to both Aβ and tau pathogenesis, and the possible bidirectional roles of neuroinflammation with AD proteinopathy have been examined. For example, initial glial activation is thought to be an early mechanism to eliminate Aβ, yet this process often leads to a vicious cycle of development of further chronic neuroinflammatory and neurotoxic damage. Specific reactive astrocytic and microglial markers, such as glial fibrillary acidic protein (GFAP) and chitinase‐3‐like protein 1 (YKL‐40), contribute to a higher risk of AD., YKL‐40 has emerged as an important candidate biomarker for examining the clinical progression of AD, and can be detected at the earliest stage of pathogenesis. Similarly, GFAP is a valuable marker in the early detection and prediction of the course of AD. Although these two markers have shown promising clinical significance in tracking AD, an existing limitation of these plasma‐based markers is that they may indicate both neuroinflammatory and systemic inflammatory processes. Comparing whether GFAP and YKL‐40 are differentially linked to Aβ and cerebrovascular burden has not yet been investigated. One marker reflecting small vessel cerebrovascular disease, broadly studied in aging and dementia, are white matter hyperintensities (WMHs), visualized as areas with increased brightness on T2‐weighted magnetic resonance imaging (MRI).