Post-Ischemic Permeability of the Blood-Brain Barrier to Amyloid and Platelets as a Factor in the Maturation of Alzheimer's Disease-Type Brain Neurodegeneration

Abstract

The aim of this review is to present evidence of the impact of ischemic changes in the blood-brain barrier on the maturation of post-ischemic brain neurodegeneration with features of Alzheimer's disease. Understanding the processes involved in the permeability of the post-ischemic blood-brain barrier during recirculation will provide clinically relevant knowledge regarding the neuropathological changes that ultimately lead to dementia of the Alzheimer's disease type. In this review, we try to distinguish between primary and secondary neuropathological processes during and after ischemia. Therefore, we can observe two hit stages that contribute to Alzheimer's disease development. The onset of ischemic brain pathology includes primary ischemic neuronal damage and death followed by the ischemic injury of the blood-brain barrier with serum leakage of amyloid into the brain tissue, leading to increased ischemic neuronal susceptibility to amyloid neurotoxicity, culminating in the formation of amyloid plaques and ending in full-blown dementia of the Alzheimer's disease type.

Keywords: Alzheimer’s disease; amyloid; amyloid plaques; astrocytes; blood–brain barrier; brain ischemia; microbleeding; neurodegeneration; neurofibrillary tangle; pericytes; platelets; tau protein.

Figure 1

Hypothetical illustration of the role of ischemic brain injury and its relationship with the ischemic blood–brain barrier (BBB) in generating Alzheimer’s disease-type neuropathology in a vicious circle. Cerebral ischemia leads to increased permeability of the BBB, which drives platelets, an amyloid protein precursor (APP), and amyloid to various structures in the brain, leading to the development of cerebral amyloid angiopathy (CAA), which results in reduced cerebral blood flow. which triggers repeated focal cerebral ischemia with increased permeability of the BBB in a vicious circle.

Figure 2

Two pathways of β-amyloid peptide formation and accumulation after ischemic brain injury and their impact on the development of amyloid plaques. Thickness of response intensity—arrows; BBB—blood–brain barrier; APP—amyloid protein precursor.