Sex and Region-Specific Disruption of Autophagy and Mitophagy in Alzheimer’S Disease: Linking Cellular Dysfunction to Cognitive Decline

Sex and Region-Specific Disruption of Autophagy and Mitophagy in Alzheimer’S Disease: Linking Cellular Dysfunction to Cognitive Decline Publisher

A Adlimoghaddam AIDA ; F Fayazbakhsh FARIBA ; M Mohammadi MOHSEN ; Z Babaei ZEINAB ; A Barzegar Behrooz AMIR ; F Tabasi FARHAD ; T Guan TENG ; I Beheshti IMAN ; M Aghaei MAHMOUD ; Dj Klionsky Daniel J

Source: Cell Death Discovery Published:2025

Abstract

Macroautophagy and mitophagy are critical processes in Alzheimer’s disease (AD), yet their links to behavioral outcomes, particularly sex-specific differences, are not fully understood. This study investigates autophagic (LC3B-II, SQSTM1) and mitophagic (BNIP3L, BNIP3, BCL2L13) markers in the cortex and hippocampus of male and female 3xTg-AD mice, using western blotting, transmission electron microscopy (TEM), and behavioral tests (novel object recognition and novel object placement). Significant sex-specific differences emerged: female 3xTg-AD mice exhibited autophagosome accumulation due to impaired degradation in the cortex, while males showed fewer autophagosomes, especially in the hippocampus, without significant degradation changes. TEM analyses demonstrated variations in mitochondrial and mitophagosome numbers correlated with memory outcomes. Females had enhanced mitophagy, with higher BNIP3L and BCL2L13 levels, whereas males showed elevated BNIP3 dimers. Cognitive deficits in females correlated with mitochondrial dysfunction in the cortex, while in males, higher LC3B-II levels associated positively with cognitive performance, suggesting protective autophagy effects. Using machine learning, we predicted mitophagosome and mitochondrial numbers based on behavioral data, pioneering a predictive approach to cellular outcomes in AD. These findings underscore the importance of sex-specific regulation of autophagy and mitophagy in AD and support personalized therapeutic approaches targeting these pathways. Integrating machine learning emphasizes its potential to advance neurodegenerative research. (Figure presented.) © 2025 Elsevier B.V., All rights reserved.

Style	Citing Format
MLA	A Adlimoghaddam AIDA, et al.. "Sex and Region-Specific Disruption of Autophagy and Mitophagy in Alzheimer’S Disease: Linking Cellular Dysfunction to Cognitive Decline." Cell Death Discovery, vol. 11, no. 1, 2025, pp. -.
APA	A Adlimoghaddam AIDA, F Fayazbakhsh FARIBA, M Mohammadi MOHSEN, Z Babaei ZEINAB, A Barzegar Behrooz AMIR, F Tabasi FARHAD, T Guan TENG, I Beheshti IMAN, M Aghaei MAHMOUD, Dj Klionsky Daniel J (2025). Sex and Region-Specific Disruption of Autophagy and Mitophagy in Alzheimer’S Disease: Linking Cellular Dysfunction to Cognitive Decline. Cell Death Discovery, 11(1), -.
Chicago	A Adlimoghaddam AIDA, F Fayazbakhsh FARIBA, M Mohammadi MOHSEN, Z Babaei ZEINAB, A Barzegar Behrooz AMIR, F Tabasi FARHAD, T Guan TENG, I Beheshti IMAN, M Aghaei MAHMOUD, Dj Klionsky Daniel J. "Sex and Region-Specific Disruption of Autophagy and Mitophagy in Alzheimer’S Disease: Linking Cellular Dysfunction to Cognitive Decline." Cell Death Discovery 11, no. 1 (2025): -.
Harvard	A Adlimoghaddam AIDA et al. (2025) 'Sex and Region-Specific Disruption of Autophagy and Mitophagy in Alzheimer’S Disease: Linking Cellular Dysfunction to Cognitive Decline', Cell Death Discovery, 11(1), pp. -.
Vancouver	A Adlimoghaddam AIDA, F Fayazbakhsh FARIBA, M Mohammadi MOHSEN, Z Babaei ZEINAB, A Barzegar Behrooz AMIR, F Tabasi FARHAD, et al.. Sex and Region-Specific Disruption of Autophagy and Mitophagy in Alzheimer’S Disease: Linking Cellular Dysfunction to Cognitive Decline. Cell Death Discovery. 2025;11(1):-.
BibTex	@article{ author = {A Adlimoghaddam AIDA and F Fayazbakhsh FARIBA and M Mohammadi MOHSEN and Z Babaei ZEINAB and A Barzegar Behrooz AMIR and F Tabasi FARHAD and T Guan TENG and I Beheshti IMAN and M Aghaei MAHMOUD and Dj Klionsky Daniel J}, title = {Sex and Region-Specific Disruption of Autophagy and Mitophagy in Alzheimer’S Disease: Linking Cellular Dysfunction to Cognitive Decline}, journal = {Cell Death Discovery}, volume = {11}, number = {1}, pages = {-}, year = {2025} }
RIS	TY - JOUR AU - A Adlimoghaddam AIDA AU - F Fayazbakhsh FARIBA AU - M Mohammadi MOHSEN AU - Z Babaei ZEINAB AU - A Barzegar Behrooz AMIR AU - F Tabasi FARHAD AU - T Guan TENG AU - I Beheshti IMAN AU - M Aghaei MAHMOUD AU - Dj Klionsky Daniel J TI - Sex and Region-Specific Disruption of Autophagy and Mitophagy in Alzheimer’S Disease: Linking Cellular Dysfunction to Cognitive Decline JO - Cell Death Discovery VL - 11 IS - 1 SP - EP - PY - 2025 ER -

Style

Citing Format

MLA

A Adlimoghaddam AIDA, et al.. "Sex and Region-Specific Disruption of Autophagy and Mitophagy in Alzheimer’S Disease: Linking Cellular Dysfunction to Cognitive Decline." Cell Death Discovery, vol. 11, no. 1, 2025, pp. -.

APA

A Adlimoghaddam AIDA, F Fayazbakhsh FARIBA, M Mohammadi MOHSEN, Z Babaei ZEINAB, A Barzegar Behrooz AMIR, F Tabasi FARHAD, T Guan TENG, I Beheshti IMAN, M Aghaei MAHMOUD, Dj Klionsky Daniel J (2025). Sex and Region-Specific Disruption of Autophagy and Mitophagy in Alzheimer’S Disease: Linking Cellular Dysfunction to Cognitive Decline. Cell Death Discovery, 11(1), -.

Chicago

A Adlimoghaddam AIDA, F Fayazbakhsh FARIBA, M Mohammadi MOHSEN, Z Babaei ZEINAB, A Barzegar Behrooz AMIR, F Tabasi FARHAD, T Guan TENG, I Beheshti IMAN, M Aghaei MAHMOUD, Dj Klionsky Daniel J. "Sex and Region-Specific Disruption of Autophagy and Mitophagy in Alzheimer’S Disease: Linking Cellular Dysfunction to Cognitive Decline." Cell Death Discovery 11, no. 1 (2025): -.

Harvard

A Adlimoghaddam AIDA et al. (2025) 'Sex and Region-Specific Disruption of Autophagy and Mitophagy in Alzheimer’S Disease: Linking Cellular Dysfunction to Cognitive Decline', Cell Death Discovery, 11(1), pp. -.

Vancouver

A Adlimoghaddam AIDA, F Fayazbakhsh FARIBA, M Mohammadi MOHSEN, Z Babaei ZEINAB, A Barzegar Behrooz AMIR, F Tabasi FARHAD, et al.. Sex and Region-Specific Disruption of Autophagy and Mitophagy in Alzheimer’S Disease: Linking Cellular Dysfunction to Cognitive Decline. Cell Death Discovery. 2025;11(1):-.

BibTex

@article{ author = {A Adlimoghaddam AIDA and F Fayazbakhsh FARIBA and M Mohammadi MOHSEN and Z Babaei ZEINAB and A Barzegar Behrooz AMIR and F Tabasi FARHAD and T Guan TENG and I Beheshti IMAN and M Aghaei MAHMOUD and Dj Klionsky Daniel J}, title = {Sex and Region-Specific Disruption of Autophagy and Mitophagy in Alzheimer’S Disease: Linking Cellular Dysfunction to Cognitive Decline}, journal = {Cell Death Discovery}, volume = {11}, number = {1}, pages = {-}, year = {2025} }

RIS

TY - JOUR
AU - A Adlimoghaddam AIDA
AU - F Fayazbakhsh FARIBA
AU - M Mohammadi MOHSEN
AU - Z Babaei ZEINAB
AU - A Barzegar Behrooz AMIR
AU - F Tabasi FARHAD
AU - T Guan TENG
AU - I Beheshti IMAN
AU - M Aghaei MAHMOUD
AU - Dj Klionsky Daniel J
TI - Sex and Region-Specific Disruption of Autophagy and Mitophagy in Alzheimer’S Disease: Linking Cellular Dysfunction to Cognitive Decline
JO - Cell Death Discovery
VL - 11
IS - 1
SP -
EP -
PY - 2025
ER -

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Abstract