Contingent Vulnerability of Entorhinal Parvalbumin-Containing Neurons in Alzheimer’s Disease

Abstract

Calcium-binding proteins containing local circuit neurons are distributed ubiquitously in the human cerebral cortex where they colocalize with a subpopulation of cells that contain GABA. Several reports using a variety of pathological models, including Alzheimer's disease (AD), have suggested that cells containing calcium-binding proteins are resistant to pathological insults. In this report, we test the hypothesis that AD pathology can differentially affect parvalbumin-containing cells depending on their location in the entorhinal cortex and the state of projection neurons with which they are associated. Using cases with different quantities of AD pathology, we determined the density of immunostaining for parvalbumin in the entorhinal cortex, and we correlated this with the concomitant pathological lesions in the various layers of this cortex. Our results show a clear decrease in parvalbumin immunostaining in some parts of the entorhinal cortex when AD neuropathological markers are present. As the density of pathological markers in the entorhinal cortex becomes greater and more widespread, there is a decrease of parvalbumin immunostaining in additional layers, although in all cases, some cells persist. Parvalbumin-containing neurons are clearly vulnerable in AD, but not because of neurofibrillary tangle formation. Instead, they are rendered vulnerable only after substantial loss of projection neurons; only then do they, too, become part of the lesion.

Excitation and Inhibition Jointly Regulate Cortical Reorganization in Adult Rats

“…A decline of parvalbumin is also observed after epileptic seizure (Kamphuis et al, 1989;Sloviter, 1989;DeFelipe et al, 1993;Schwaller et al, 2004), in schizophrenia (Eyles et al, 2002;Zhang and Reynolds, 2002;Sakai et al, 2008), and in Alzheimer's disease (Solodkin et al, 1996). Under all these conditions, the decrease of parvalbumin indicates a change in the neuronal network, but, as far as we know, we here describe for the first time a change of parvalbumin immunoreactivity that correlates with changes in a topographic map.…”

Aging-related changes in calcium-binding proteins in rat perirhinal cortex

“…For example, individuals diagnosed with AD have significantly fewer CB-ir neurons in frontal, temporal and parietal cortices (Ichimiya et al, 1988; Lally et al, 1997; Mikkonen et al, 1999). AD patients also tend to have well-preserved levels of PV- and CR-immunoreactivity in several cortical areas (Brion and Resibois, 1994; Hof et al, 1991; Solodkin et al, 1996). Recent data using transgenic mice that express human amyoid precursor proteins (hAPP) and amyloid-β peptides (Aβ) further suggest a direct link between calbindin expression, AD pathology, and cognitive decline.…”

Alterations of Interneurons of the Gerbil Hippocampus after Transient Cerebral Ischemia: Effect of Pitavastatin

“…On the other hand, other studies suggest that PV-immunoreactive neurons were gradually depleted in the brain of gerbils after a longer period of ischemia (Fukuda et al, 1993). Furthermore, PV-containing neurons are supposed to be selectively vulnerable in Alzheimer's disease (Solodkin et al, 1996) and not to be protected in some forms of epilepsy (Bouilleret et al, 2000). Thus, much evidence for the vulnerability and role of PV-containing neurons to stress response such as ischemia and epilepsy is contradictory.…”