Evidence of angiogenic vessels in Alzheimer's disease.

Alterations in the blood brain barrier and brain vasculature may be involved in neurodegeneration and neuroinflammation. We sought to determine if vascular remodeling characterized by angiogenic vessels or increased vascular density, occurred in pathologically confirmed Alzheimer's disease (AD) postmortem human brain tissues. We examined brains of deceased, older catholic clergy from the Religious Order Study, a longitudinal clinical-pathological study of aging and AD. The hippocampus, midfrontal cortex, substantia nigra, globus pallidus and locus ceruleus were examined for integrin alphavbeta3 immunoreactivity, a marker of angiogenesis, and vascular densities. Activated microglia cell counts were also performed. All areas except the globus pallidus exhibited elevated alphavbeta3 immunoreactivity in AD cases compared with controls. Only in the hippocampus did the ongoing angiogenesis result in increased vascular density compared with controls. Vascular density was correlated with Abeta load in the hippocampus and alphavbeta3 reactivity was correlated with neurofibrillary tangles in the midfrontal cortex and in the substantia nigra. These data indicate that ongoing angiogenesis is present in brain regions affected by AD pathology and may be related to tissue injury.

Blood-brain barrier pathology in Alzheimer's and Parkinson's disease: implications for drug therapy.

The blood-brain barrier (BBB) is a tightly regulated barrier in the central nervous system. Though the BBB is thought to be intact during neurodegenerative diseases such as Alzheimer's (AD) and Parkinson's disease (PD), recent evidence argues otherwise. Dysfunction of the BBB may be involved in disease progression, eliciting of peripheral immune response, and, most importantly, altered drug efficacy. In this review, we will give a brief overview of the BBB, its components, and their functions. We will critically evaluate the current literature in AD and PD BBB pathology resulting from insult, neuroinflammation, and neurodegeneration. Specifically, we will discuss alterations in tight junction, transport and endothelial cell surface proteins, and vascular density changes, all of which result in altered permeability. Finally, we will discuss the implications of BBB dysfunction in current and future therapeutics. Developing a better appreciation of BBB dysfunction in AD and PD may not only provide novel strategies in treatment, but will prove an interesting milestone in understanding neurodegenerative disease etiology and progression.