Neurobiology of diseaseOct 30, 2025

Mitochondrial Cleanup in Alzheimer's Disease and Its Possible Use for Treatment

Alzheimers & Treatments Weekly Brief ↗PubMed ↗DOI ↗

Updated Jan 2, 2026

Abstract

Accumulation of damaged mitochondria is a hallmark of age-related neurodegenerative disorders, including Alzheimer's disease (AD).

Mitophagy, the process of removing damaged mitochondria, may play a significant role in the progression of Alzheimer's disease.
Deficits in mitophagy could interact with amyloid-β and Tau pathology, potentially leading to increased neuronal damage.
Mitochondrial dysfunction may worsen Alzheimer's by activating the NLRP3 inflammasome, which is associated with inflammation in the brain.
Modulating mitophagy could provide neuroprotection by reducing inflammation in neurons and microglia.
Pathological ferroptosis may be a key driver of Alzheimer's, with mitophagy showing a complex role in this process.

Simplified

Accumulation of damaged mitochondria is a well-established hallmark of age-related neurodegenerative disorders, including Alzheimer's disease (AD). Increasing evidence suggests that mitophagy, a selective autophagic degradation of damaged mitochondria, plays an important role in AD progression. The interaction between mitophagy deficits and amyloid-β (Aβ) or Tau pathology may establish a vicious cycle that ultimately results in neuronal damage and death. Mitochondrial dysfunction exacerbates AD pathogenesis by activating the NLRP3 inflammasome, whereas modulation of mitophagy may confer neuroprotection by attenuating inflammation in neurons and microglia. Pathological ferroptosis has emerged as a potential key driver of AD, with mitophagy intriguingly demonstrating a dual role in this process. In this review, we elucidate the molecular mechanisms underlying mitophagy and its involvement in AD, thereby providing insights into AD pathogenesis. We further highlight the therapeutic potential of targeting mitophagy as a promising strategy for AD intervention.

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Declaration of competing interest The authors declare no conflicts of interest.

PubMed

Mitochondrial Cleanup in Alzheimer's Disease and Its Possible Use for Treatment

Abstract

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