The blood-brain barrier (BBB) is involved in the pathogenesis of Alzheimer's disease (AD). BBB is a highly selective semipermeable structural and chemical barrier which ensures a stable internal environment of the brain and prevents foreign objects invading the brain tissue. BBB dysfunction induces the failure of Aβ transport from brain to the peripheral circulation across the BBB. Especially, decreased levels of LRP-1 (low density lipoprotein receptor-related protein 1) and increased levels of RAGE (receptor for advanced glycation endproducts) at the BBB can cause the failure of Aβ transport. The pathogenesis of AD is related to the BBB structural components, including pericytes, astrocytes, vascular endothelial cells, and tight junctions. BBB dysfunction will trigger neuroinflammation and oxidative stress, then enhance the activity of β-secretase and γ-secretase, and finally promote Aβ generation. A progressive accumulation of Aβ in brain and BBB dysfunction may become a feedback loop that gives rise to cognitive impairment and the onset of dementia. The correlation between BBB dysfunction and tau pathology has been well-reported. Therefore, regulating BBB function may be a new therapeutic target for treating AD.

The past several decades have given rise to more insights into the role of astrocytes in normal brain function and diseases. Astrocytes elicit an effect which may be neuroprotective or deleterious in the process of Alzheimer's disease (AD). Impairments in astrocytes and their other functions, as well as physiological reactions of astrocytes to external injury, can trigger or exacerbate hyperphosphorylated tau and amyloid-beta (Aβ) pathologies, leading to the formation of both amyloid plaques and neurofibrillary tangles (NFTs), as well as neuronal dysfunction. This review addresses the involvement of astrocytes in the Aβ pathology, where the main mechanisms include the generation and clearance of Aβ, and the formation of NFTs. It is also discussed that metabolic dysfunction from astrocytes acts as an initiating factor in the pathogenesis of AD and a contributor to the onset and development of clinical presentation in AD.

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Alzheimer’s Disease (AD) is a progressive neurodegenerative disease with irreversible cognitive impairment. So far, successful treatment and prevention for this disease are deficient in spite of delaying the progression of cognitive impairment and dementia. Cyclin dependent kinase 5 (Cdk5), a unique member of the cyclin-dependent kinase family, is involved in AD pathogenesis and may be a pathophysiological mediator that links the major pathological features of AD. Cdk5 dysregulation interferes with the proteolytic processing of Amyloid-beta Protein Precursor (APP) and modulates amyloidbeta (Aβ) by affecting three enzymes called α-, β- and γ-secretase, which are critical for the hydrolysis of APP. Given that the accumulation and deposition of Aβ derived from APP are a common hinge point in the numerous pathogenic hypotheses of AD, figuring out that influence of specific mechanisms of Cdk5 on Aβ pathology will deepen our understanding of AD.

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