Molecular neurobiologyAug 1, 2026

How Waste Removal and Inflammation in Brain Support Cells Are Linked in Alzheimer's Disease

Longevity & Aging Weekly Brief ↗PubMed ↗DOI ↗

Updated Aug 3, 2026

Abstract

Impairment of the glial autophagy-lysosomal pathway (ALP) is critically linked to neuroinflammatory responses in Alzheimer's disease.

Glial cells play a pivotal role in regulating immune responses in the central nervous system.
Dysregulation of the glial ALP is associated with amyloid buildup and tau hyperphosphorylation in Alzheimer's disease.
Alterations in glial function may lead to synaptic impairment and white matter damage.
Key signaling pathways involved in glial ALP regulation include TFEB, mTOR, and NLRP3.
Therapeutic strategies could focus on restoring lysosomal function and modulating inflammation.
Emerging biomarkers related to ALP may assist in early diagnosis and monitoring treatment responses.

Simplified

Recent studies suggest that impairment of the glial autophagy-lysosomal pathway (ALP) critically contributes to the sustained neuroinflammatory response and neurodegenerative processes in Alzheimer's disease (AD). Glial cells, comprising microglia, astrocytes, oligodendrocytes, and ependymal cells, serve as key immune regulators in the central nervous system, where they are essential for maintaining ALP homeostasis, promoting proteostasis, and modulating neuroinflammatory responses. Here, we systematically review the regulatory roles of glial ALP in AD pathology, emphasizing its involvement in amyloid accumulation, tau hyperphosphorylation, synaptic impairment, white matter damage, and mitochondrial as well as other organelle dysfunction, and provide an in-depth analysis of key signaling pathways including TFEB, mTOR, and NLRP3. Furthermore, we outline therapeutic strategies aimed at restoring lysosomal function, regulating autophagic flux, and suppressing inflammation, along with a discussion of the multi-target regulatory potential of acupuncture and natural bioactive agents. We also highlight emerging ALP-associated biomarkers and their potential utility in early diagnosis and treatment response assessment. The objective of this review is to uncover the mechanistic interplay between glial ALP dysregulation and the pathological cascade of AD, offering a conceptual framework for the development of novel therapeutics that integrate neuroprotection with immune modulation.

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Competing interests

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.

PubMed

How Waste Removal and Inflammation in Brain Support Cells Are Linked in Alzheimer's Disease

Abstract

Full Text

Funding

Competing interests

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