Cerebral microinfarct is emergency consequence of Alzheimer's disease: a new insight into development of neurodegenerative diseases

Abstract

Imbalance of Aβ and tau protein production and clearance are the key factors among many causes of Alzheimer's disease that leading to neurons degeneration and cognitive disorders. As a novel approach, glymphatic system quickly clear metabolic waste (especially Aβ and tau) from cerebral environment, and dysfunction of glymphatic system may relate to occurrence of Alzheimer's disease. Microinfarct is a common histopathologic situation occurring in aging brain and leads to dramatic increase the generation of metabolic by-product after neuronal injury, hindering the operation of glymphatic system and suppress cerebral spinal fluid (CSF) and cerebral interstitial fluid (interstitial fluid, ISF) exchange. Microinfarcts destruct the integrity of microvascular and microstructural tissue, result in Aβ deposition and tau phosphorylation that form neurofibrillary tangles and associated with the cause of Alzheimer's disease. Currently, it has been found that glymphatic system is involved in the pathological process of Alzheimer's disease. Improving the function of glymphatic system after cerebral microinfarcts could be developed as a new approach for Alzheimer's disease prevention and treatment. In this review, we will provide in-depth discussion on functional changes of glymphatic system after cerebral microinfarcts, further reveal pathogenesis of Alzheimer's disease and provide a potentially more effective method for treatment of Alzheimer's disease.

Alzheimer’s Disease: Understanding Its Novel Drug Delivery Systems and Treatments

“…The antibodies are primarily focused on extracellular tau, which is transmitted from cell to cell in a prion-like fashion. Several tau monoclonal antibodies, including semorinemab, zagotenemab, and gosuranemab, have failed to show a drug-placebo difference in recent Alzheimer's disease studies [ 10 ].…”

Facile synthesis of a fluorescent probe based on a terbium-based metal–organic framework for selective detection of Fe(iii) and Al(iii)

“…11,12 Most seriously, Al 3+ is extremely harmful to the human body, increasing the risk of Parkinson's disease, breast cancer and Alzheimer's disease. [13][14][15] Therefore, it is imperative to develop a sensitive and robust analytical method to detect the concentrations of Fe 3+ and Al 3+ .…”

Detrimental Effects of ApoE ε4 on Blood–Brain Barrier Integrity and Their Potential Implications on the Pathogenesis of Alzheimer’s Disease

“…Recent evidence from animal and human studies suggests that cerebrovascular dysfunctions, leading to blood-brain barrier (BBB) leakage, might also be associated with ApoE ε4 and AD pathology [13][14][15]. For instance, cerebral microinfarcts and microbleeds, which are associated with the disruption of structural connections in the brain [16], represent a common pathological feature in patients with dementia and cerebrovascular diseases [17]. The association between cerebrovascular dysfunctions and AD pathology is further supported by the joint risk factor profile of AD and cardiovascular diseases consisting of the ApoE ε4 genotype, diabetes, hypoperfusion, hypertension and hypercholesterolemia [15].…”