The road to clarity for postischemic
dementia mechanisms has been one fraught with a wide range of complications and numerous revisions with a lack of a final
solution. Importantly,
brain ischemia is a leading cause of death and
cognitive impairment worldwide. However, the mechanisms of progressive
cognitive decline following
brain ischemia are not yet certain. Data from animal models and clinical pioneering studies of
brain ischemia have demonstrated an increase in expression and processing of
amyloid precursor
protein to a
neurotoxin oligomeric β-
amyloid peptide. Functional and memory brain restoration after ischemic
brain injury is delayed and incomplete due to a lesion related increase in the amount of the
neurotoxin amyloid protein. Moreover, ischemic injury is strongly accelerated by aging, too. In this review, we will present our current thinking about biogenesis of
amyloid from the
amyloid precursor
protein in ischemic
brain injury, and how this factor presents etiological, therapeutic and diagnostic targets that are now under consideration. Progressive injury of the ischemic brain parenchyma may be caused not only by degeneration of selectively vulnerable neurons destroyed during
ischemia but also by acute and chronic damage of resistant areas of the brain and progressive damage in the blood-brain barrier. We propose that in postischemic
dementia an initial ischemic injury precedes the cerebrovascular and brain parenchyma accumulation of
Alzheimer disease related
neurotoxin β-
amyloid peptide, which in turn amplifies the neurovascular dysfunction triggering focal ischemic episodes as a vicious cycle preceding final neurodegenerative pathology. Persistent ischemic blood-brain barrier insufficiency with accumulation of
neurotoxin β-
amyloid protein in the brain tissue, especially in extracellular perivascular space and blood-brain barrier microvessels, may gradually, over a lifetime, progress to brain
atrophy and to full-blown ischemic
dementia with Alzheimer phenotype.