Stereologic Analysis of Microvascular Morphology in the Elderly

Abstract

The presence of microvascular changes has been documented both in brain aging and Alzheimer disease (AD), although the relationship between the morphometry of brain capillaries and cognitive impairment is still unknown. We performed an analysis of capillary morphometric parameters and AD-related pathology in 19 elderly individuals with variable degrees of cognitive decline. Cognitive status was assessed prospectively using the Clinical Dementia Rating (CDR) scale. Total capillary lengths and numbers as well as mean length-weighted diameter, total neurofibrillary tangle (NFT) and neuron numbers, and amyloid volume were estimated in entorhinal cortex and the CA1 field. Total capillary numbers and mean diameters explained almost 40% of the neuron number variability in both the CA1 and entorhinal cortex. Total capillary length and numbers in the CA1 and entorhinal cortex did not predict cognitive status. Mean capillary diameters in the CA1 and entorhinal cortex were significantly related to CDR scores, explaining 18.5% and 31.1% of the cognitive variability, respectively. This relationship persisted after controlling for NFT and neuron numbers in multivariate regression models. Consistent with the growing interest about microvascular pathology in brain aging, the present data indicate that changes in capillary morphometric parameters may represent independent predictors of AD-related neuronal depletion and cognitive decline.

Human Umbilical Vein Endothelial Cells Protect Against Hypoxic-Ischemic Damage in Neonatal Brain via Stromal Cell-derived Factor 1/C-X-C Chemokine Receptor Type 4

“…17 The region containing the highest vessel density was chosen. Three visual fields were acquired (20× magnification) to calculate the length density.…”

B-vitamin deficiency causes hyperhomocysteinemia and vascular cognitive impairment in mice

“…However, this has been difficult to establish, not the least because of poor consensus on neuropathological methods of classifying and quantifying cerebrovascular lesions (1,22). Recent advances in unbiased stereology (23) now provide a rigorous and objective (albeit tedious) method of quantifying structural parameters of the microvasculature in postmortem human (24) and animal brains (25). However, vascular and cognitive outcomes have not yet been correlated by these methods.…”

Stereologic estimates of total spinophilin-immunoreactive spine number in area 9 and the CA1 field: Relationship with the progression of Alzheimer's disease

“…Specific labeling was revealed with an horseradish peroxidaseconjugated anti-mouse antibody (1:100; Dako, Glostrup, Denmark), and 3,3'-diaminobenzidine as a chromogen. The sections were then counterstained with cresyl violet for stereologic determination of unaffected neurons (i.e., neurons stained only by cresyl violet), neurons with intracellular NFT, and extracellular (ghost) NFT [3,6,7,28]. In all cases, antibody AT8 penetrated through the full depth of the sections.…”

“…Sections were processed for Nissl staining with cresyl violet, and coverslipped with DePex (Fluka, Milwaukee, WI, USA). All of the staining procedures were already used in our previous stereological studies [3,75].…”