RT Journal Article
T1 Distinct disease-sensitive GABAergic neurons in the perirhinal cortex of Alzheimer's mice and patients
A1 Sánchez-Mejías, Elisabeth
A1 Núñez-Díaz, Cristina
A1 Sánchez-Varo, Raquel María
A1 Gómez-Arboledas, Ángela
A1 García-León, Juan Antonio
A1 Fernández-Valenzuela, Juan José
A1 Mejías-Ortega, Marina
A1 Trujillo-Estrada, Laura Isabel
A1 Baglietto-Vargas, David
A1 Moreno-González, Inés
A1 Dávila-Cansino, José Carlos
A1 Vitorica Ferrández, Javier
A1 Gutiérrez-Pérez, Antonia
K1 Alzheimer, Enfermedad de
AB Neuronal loss is the best neuropathological substrate that correlates with cortical atrophy and dementia in Alzheimer's disease (AD). Defective GABAergic neuronal functions may lead to cortical network hyperactivity and aberrant neuronal oscillations and in consequence, generate a detrimental alteration in memory processes. In this study, using immunohistochemical and stereological approaches, we report that the two major and non-overlapping groups of inhibitory interneurons (SOM-cells and PV-cells) displayed distinct vulnerability in the perirhinal cortex of APP/PS1 mice and AD patients. SOM-positive neurons were notably sensitive and exhibited a dramatic decrease in the perirhinal cortex of 6-month-old transgenic mice (57% and 61% in areas 36 and 35, respectively) and, most importantly, in AD patients (91% in Braak V-VI cases). In addition, this interneuron degenerative process seems to occur in parallel, and closely related, with the progression of the amyloid pathology. However, the population expressing PV was unaffected in APP/PS1 mice while in AD brains suffered a pronounced and significant loss (69%). As a key component of cortico-hippocampal networks, the perirhinal cortex plays an important role in memory processes, especially in familiarity-based memory recognition. Therefore, disrupted functional connectivity of this cortical region, as a result of the early SOM and PV neurodegeneration, might contribute to the altered brain rhythms and cognitive failures observed in the initial clinical phase of AD patients. Finally, these findings highlight the failure of amyloidogenic AD models to fully recapitulate the selective neuronal degeneration occurring in humans.
PB Wiley
YR 2020
FD 2020-03
LK https://hdl.handle.net/10630/29420
UL https://hdl.handle.net/10630/29420
LA eng
NO Sanchez-Mejias E, Nuñez-Diaz C, Sanchez-Varo R, Gomez-Arboledas A, Garcia-Leon JA, Fernandez-Valenzuela JJ, Mejias-Ortega M, Trujillo-Estrada L, Baglietto-Vargas D, Moreno-Gonzalez I, Davila JC, Vitorica J, Gutierrez A. Distinct disease-sensitive GABAergic neurons in the perirhinal cortex of Alzheimer's mice and patients. Brain Pathol. 2020 Mar;30(2):345-363
DS RIUMA. Repositorio Institucional de la Universidad de Málaga
RD 20 ene 2026