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Review
. 2024 Dec 16:18:1503069.
doi: 10.3389/fnins.2024.1503069. eCollection 2024.

Olfactory deficits in aging and Alzheimer's-spotlight on inhibitory interneurons

Kaoutar Elhabbari  1 , Siran Sireci  1 , Markus Rothermel  1 , Daniela Brunert  1
Affiliations
Review

Olfactory deficits in aging and Alzheimer's-spotlight on inhibitory interneurons

Kaoutar Elhabbari et al. Front Neurosci. .

Abstract

Cognitive function in healthy aging and neurodegenerative diseases like Alzheimer's disease (AD) correlates to olfactory performance. Aging and disease progression both show marked olfactory deficits in humans and rodents. As a clear understanding of what causes olfactory deficits is still missing, research on this topic is paramount to diagnostics and early intervention therapy. A recent development of this research is focusing on GABAergic interneurons. Both aging and AD show a change in excitation/inhibition balance, indicating reduced inhibitory network functions. In the olfactory system, inhibition has an especially prominent role in processing information, as the olfactory bulb (OB), the first relay station of olfactory information in the brain, contains an unusually high number of inhibitory interneurons. This review summarizes the current knowledge on inhibitory interneurons at the level of the OB and the primary olfactory cortices to gain an overview of how these neurons might influence olfactory behavior. We also compare changes in interneuron composition in different olfactory brain areas between healthy aging and AD as the most common neurodegenerative disease. We find that pathophysiological changes in olfactory areas mirror findings from hippocampal and cortical regions that describe a marked cell loss for GABAergic interneurons in AD but not aging. Rather than differences in brain areas, differences in vulnerability were shown for different interneuron populations through all olfactory regions, with somatostatin-positive cells most strongly affected.

Keywords: Alzheimer’s disease; aging; inhibition; interneurons; olfaction.

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Conflict of interest statement

The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest. The author(s) declared that they were an editorial board member of Frontiers, at the time of submission. This had no impact on the peer review process and the final decision.

Figures

Figure 1
Figure 1
Distribution of interneuron markers in primary and secondary olfactory areas. (A) Example pictures from the Allen Mouse Brain Atlas showing coronal brain sections containing olfactory areas in reference to Nissl staining of these regions. Images were derived from Allen Mouse Brain Atlas and Allen Reference Atlas, Experiment 77869074 (https://mouse.brain-map.org/experiment/show/77869074) for cholecystokinin (cck), Experiment 1001 (https://mouse.brain-map.org/experiment/show/1001) for somatostatin (sst), and Experiment 71717640 (https://mouse.brain-map.org/experiment/show/71717640) for calbindin (calb1) (Allen Institute for Brain Science, 2004; Lein et al., 2007). (B) Overview on the distribution of the most common interneuron markers. Data points represent estimates from ISH experiments from the Allen Mouse Brain Atlas but have been matched to reports of protein expression as far as these data are available. pv, parvalbumin; sst, somatostatin; vip, vasoactive intestinal peptide; cr, calretinin; cb, calbindin; npy, neuropeptide y; cck, cholecystokinin.
Figure 2
Figure 2
Alzheimer’s Disease (A) and aging (B) derived changes of interneuron numbers in different olfactory areas. AON, anterior olfactory nucleus; CoA, cortical amygdala; EPL, external plexiform layer; GL, glomerular layer; Grl, granule cell layer; iPL, internal plexiform layer; ML, mitral cell layer; OB, Olfactory bulb; OT, olfactory tubercle; PC, piriform cortex; LEC, lateral entorhinal cortex.
See this image and copyright information in PMC

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