Parvalbumin-immunoreactive neurons in the hippocampal formation of Alzheimer's diseased brain

doi:10.1016/S0306-4522(97)00068-7

Neuroscience

Volume 80, Issue 4, 11 August 1997, Pages 1113-1125

https://doi.org/10.1016/S0306-4522(97)00068-7 Get rights and content

Abstract

The number and topographic distribution of immunocytochemically stained parvalbumin interneurons was determined in the hippocampal formation of control and Alzheimer's diseased brain. In control hippocampus, parvalbumin interneurons were aspiny and pleomorphic, with extensive dendritic arbors. In dentate gyrus, parvalbumin cells, as well as a dense plexus of fibers and puncta, were associated with the granule cell layer. A few cells also occupied the molecular layer. In strata oriens and pyramidale of CA1–CA3 subfields, parvalbumin neurons gave rise to dendrites that extended into adjacent strata. Densely stained puncta and beaded fibers occupied stratum pyramidale, with less dense staining in adjacent strata oriens and radiatum. Virtually no parvalbumin profiles were observed in stratum lacunosum-moleculare or the alveus. Numerous polymorphic parvalbumin neurons and a dense plexus of fibers and puncta characterized the deep layer of the subiculum and the lamina principalis externa of the presubiculum. In Alzheimer's diseased hippocampus, there was an approximate 60% decrease in the number of parvalbumin interneurons in the dentate gyrus/CA4 subfield (P<0.01) and subfields CA1–CA2 (P<0.01). In contrast, parvalbumin neurons did not statistically decline in subfields CA3, subiculum or presubiculum in Alzheimer's diseased brains relative to controls. Concurrent staining with Thioflavin-S histochemistry did not reveal degenerative changes within parvalbumin-stained profiles. These findings reveal that parvalbumin interneurons within specific hippocampal subfields are selectively vulnerable in Alzheimer's disease. This vulnerability may be related to their differential connectivity, e.g., those regions connectionally related to the cerebral cortex (dentate gyrus and CA1) are more vulnerable than those regions connectionally related to subcortical loci (subiculum and presubiculum).

Section snippets

Tissue preparation

Eight human brains with no history of neurological or neuropsychological illness (mean age 64.2±6.2 years, range 28–81 years) and 12 brains of clinically diagnosed and pathologically confirmed25, 29AD (mean age 81.2±2.0 years, range 69–89 years) were obtained at autopsy (mean post-mortem delay: aged controls, 4.75±0.8 h; AD, 4.5±0.4 h; Table 1). The brains were sliced transversely into 1-cm slabs, immersion fixed for 24 h in cold (4°C) 0.1 M phosphate-buffered–4% paraformaldehyde (pH 7.4) and then

Results

We followed the cytoarchitectural subdivisions of the hippocampal formation defined by Ramon y Cajal[36]and Lorente de No[27]as previously reported.[6]In brief, the hippocampal formation consists of the dentate gyrus along the medial edge of the temporal lobe, with subfields of the hippocampus proper emanating from the hilus of the dentate gyrus (CA4), progressing through subfields CA3, CA2 and CA1 to the subiculum and adjacent presubiculum (Fig. 1a).

Parvalbumin immunostaining was observed

Discussion

This report demonstrates the selective vulnerability of parvalbumin-immunoreactive neurons within hippocampal subfields of AD brain. When interpreting the results in the context of neural systems, the present study is consistent with previous reports of both resistance and vulnerability of the parvalbumin neuronal population in AD. These findings support and expand previous neuropathological data on the predilection of certain hippocampal subfields to degeneration in AD.6, 21

Acknowledgements

We thank L. Sue, G. Binskin and J. Schaller for excellent technical assistance. We are indebted to the families whose donation of brain tissue is the basis of this report. Supported by NS 26146, AG 10688, AG 11482, AG 09466 and AG 10161.

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Parvalbumin-immunoreactive neurons in the hippocampal formation of Alzheimer's diseased brain

Abstract

Section snippets

Tissue preparation

Results

Discussion

Acknowledgements

Brain Res.

Neuroscience

Neurosci. Lett.

J. neurol. Sci.

Neurosci. Lett.

Neuroscience

Brain Res.

J. neurol. Sci.

Neurosci. Lett.

J. neurol. Sci.

Peptides

Brain Res.

Neurosci. Lett.

Brain Res.

Peptide

Transmitter systems in the primate dentate gyrus

Hum. Neurobiol.

Parvalbumin in human brain

J. Neurochem.

Parvalbumin-immunoreactive structures in the hippocampus of the human adult

Cell Tissue Res.

Amygdaloid pathology in Alzheimer's disease: qualitative and quantitative analysis

Dementia

Alz50 immunoreactive neuropil differentiates hippocampal complex subfields in Alzheimer's disease

J. comp. Neurol.

Parvalbumin in most γ-aminobutyric acid-containing neurons of the rat cerebral cortex

Science

Somatostatin immunoreactive neurons in the human hippocampus and cortex shown by immunogold/silver intensification on vibratome sections: coexistence with neuropeptide Y neuronism, and effects in Alzheimer-type dementia

J. comp. Neurol.