The Parahippocampal Gyrus in Alzheimer's Disease: Clinical and Preclinical Neuroanatomical Correlates

Abstract

The human parahippocampal gyrus forms a large part of the limbic lobe along the ventromedial part of the temporal cortical mantle. It is a variable and complicated cortex in terms of structure, and the latter is aggravated further by interfaces with the anterior insula anteriorly and the cingulate gyrus and occipital lobe posteriorly. Additional complications relate to its lateral border with the temporal cortex and especially the sulcal configurations that define this junction. The rhinal sulcus, which separates parahippocampal and temporal cortices in other species, including the anthropoid apes, is either lacking or rudimentary in the human brain. Thus, defining this junction requires cytoarchitectural examination and precludes the use of mere inspection of sulcal existing patterns. The cortical areas that form the parahippocampal gyrus are vulnerable to pathological changes in Alzheimer's disease (AD), and its entorhinal and perirhinal subdivisions are both the most heavily damaged cortical areas and the focus for disease onset. The neurons that acquire neurofibrillary tangles (NFTs) occupy the junction of the isocortical mantle with the limbic cortical mantle, but share, or partially share, a vulnerability phenotype with large neurons in both domains. The differential expression of this phenotype across time creates the false impression of NFT spread in crosssectional comparisons of AD brains. The questions of what this phenotype is and why it is expressed first in the perirhinal and entorhinal cortices of the parahippocampal gyrus are the central molecular biological/neuroanatomical questions in understanding the etiology of AD.

Comparison of manual direct and automated indirect measurement of hippocampus using magnetic resonance imaging

“…As the substructures of the medial temporal lobe (hippocampus, parahippocampal gyrus, and entorhinal cortex) are known to be affected very early in the course of the disease, even years before the onset of clinical symptoms [1][2][3], the availability of an observer-independant method that facilitates the reliable assessment of structural alterations in this area would be very helpful for both research and clinical purposes.…”

“…Neuropathological research has shown that brain degeneration occurs very early in the course of the disease, even before the onset of clinical symptoms, and predominantly affects certain areas, particularly the substructures of the medial temporal lobe [1][2][3]. Previous neuroimaging studies reported significant atrophy of the hippocampus [4][5][6][7], the parahippocampal gyrus [8] and the entorhinal cortex [6,7,[9][10][11][12] in subjects with mild cognitive impairment and AD.…”

Disrupted Functional and Structural Networks in Cognitively Normal Elderly Subjects with the APOE ɛ4 Allele

“…In addition to the observed global properties, APOE e4 related regional WM network changes were identified in the SFGdor.R, ACG.L, PHG.R, and IOG.L. The PHG has been strongly implicated in AD pathophysiology (Van Hoesen et al, 2000) and associated with the APOE e4 allele (Honea et al, 2009;Nierenberg et al, 2005). Post-mortem studies have demonstrated a severe neuronal loss in the entorhinal cortex (PHG contains most of the entorhinal cortex) even in very mild AD (Hyman et al, 1984) and mild cognitive impairments (MCI) (Kordower et al, 2001).…”

Differential effects of aging and Alzheimer's disease on medial temporal lobe cortical thickness and surface area

“…Although boundaries defined by macroscopic anatomical features do not correspond perfectly to microscopic histologic subdivisions (Amunts et al, 2005), this approach has been useful in the in vivo measurement of entorhinal atrophy in early clinical and incipient phases of Alzheimer's disease (AD) (Killiany et al, 2000;Xu et al, 2000;de Leon et al, 2001;Dickerson et al, 2001;Du et al, 2001). The entorhinal and perirhinal cortices are devastated by neurofibrillary pathology and cell loss very early in the course of AD (Hyman et al, 1984;Braak and Braak, 1991;Price et al, 1991;Gomez-Isla et al, 1996;Van Hoesen et al, 2000;Kordower et al, 2001). The posterior parahippocampal cortex caudal to these regions appears to be less affected, and demonstrates pathologic change in somewhat more advanced stages of the disease.…”