From Genetics to Neuroinflammation: The Impact of ApoE4 on Microglial Function in Alzheimer’s Disease

Cells, Год журнала: 2025, Номер 14(4), С. 243 - 243

Опубликована: Фев. 7, 2025

Alzheimer’s disease (AD) is a debilitating neurodegenerative disorder marked by progressive cognitive decline and memory loss, impacting millions of people around the world. The apolipoprotein E4 (ApoE4) allele most prominent genetic risk factor for late-onset AD, dramatically increasing susceptibility accelerating onset compared to its isoforms ApoE2 ApoE3. ApoE4’s unique structure, which arises from single-amino-acid changes, profoundly alters function. This review examines critical interplay between ApoE4 microglia—the brain’s resident immune cells—and how this relationship contributes AD pathology. We explore molecular mechanisms modulates microglial activity, promoting pro-inflammatory state, impairing phagocytic function, disrupting lipid metabolism. These changes diminish microglia’s ability clear amyloid-beta peptides, exacerbating neuroinflammation leading neuronal damage synaptic dysfunction. Additionally, adversely affects other glial cells, such as astrocytes oligodendrocytes, further compromising support myelination. Understanding ApoE4–microglia axis provides valuable insights into progression reveals potential therapeutic targets. discuss current strategies modulate function using small molecules, antisense oligonucleotides, gene editing technologies. Immunotherapies targeting ApoE4, along with neuroprotective approaches enhance survival, are also examined. Future directions highlight importance personalized medicine based on individual ApoE genotypes, early biomarker identification assessment, investigating role in diseases. emphasizes intricate connection dysfunction, highlighting necessity pathway develop effective interventions. Advancing our understanding area holds promise mitigating improving outcomes those affected relentless disease.

Язык: Английский

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Glucose Metabolic Reprogramming in Microglia: Implications for Neurodegenerative Diseases and Targeted Therapy

Molecular Neurobiology, Год журнала: 2025, Номер unknown

Опубликована: Фев. 22, 2025

Язык: Английский

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Age-Related Neurodegenerative Diseases: A Stem Cell’s Perspective

Cells, Год журнала: 2025, Номер 14(5), С. 347 - 347

Опубликована: Фев. 27, 2025

Neurodegenerative diseases encompass a number of very heterogeneous disorders, primarily characterized by neuronal loss and concomitant decline in neurological function. Examples this type clinical condition are Alzheimer's Disease, Parkinson's Huntington's Disease Amyotrophic Lateral Sclerosis. Age has been identified as major risk the etiology these which explains their increased incidence developed countries. Unfortunately, despite continued intensive efforts, no cure yet found for any diseases; reliable markers that allow an early diagnosis disease identification key molecular events leading to onset progression lacking. Altered adult neurogenesis appears precede appearance severe symptoms. Given scarcity human samples considerable differences with model species, increasingly complex stem-cell-based models being developed. These shedding light on alterations contribute development, facilitating new targets providing screening platform testing candidate drugs. Moreover, secretome other promising features cell types explored, use them replacement cells high plasticity or co-adjuvant therapy combinatorial treatments.

Язык: Английский

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The effect of C-reactive protein and interleukin-3 on mild cognitive impairment with APOE ɛ4

Journal of Alzheimer s Disease, Год журнала: 2025, Номер unknown

Опубликована: Апрель 22, 2025

Background The apolipoprotein E ε4 allele ( APOE ε4) and inflammation are associated with Alzheimer's disease (AD) pathology. Mild cognitive impairment (MCI) is considered the preclinical early stage of AD. However, comprehensive effects inflammatory mediators on MCI patients specific genotypes remain poorly understood. Objective Our study aimed to explore how different numbers alleles affect plasma C-reactive protein (CRP) interleukin-3 (IL-3) levels their associations brain structure. Methods A total 339 from Disease Neuroimaging Initiative were enrolled. We compared concentrations CRP IL-3, performance, cerebrospinal fluid (CSF) AD biomarkers across genotypes. Structural magnetic resonance imaging was utilized measure gray matter volume outcomes. Pearson correlation analysis used between above indicators. Results Plasma increased in carriers, but IL-3 expression notably decreased, homozygous state most significant. negative several abilities observed only homozygotes. Additionally, a positive scores, CSF biomarker confirmed Imaging data demonstrated that right middle frontal gyrus non-carriers. Conclusions peripheral mediators’ effect function structure differs based carrier status.

Язык: Английский

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Variable and interactive effects of Sex, APOE ε4 and TREM2 on the deposition of tau in entorhinal and neocortical regions.

Research Square (Research Square), Год журнала: 2024, Номер unknown

Опубликована: Авг. 9, 2024

The canonical AD pathological cascade posits that the accumulation of amyloid beta (Aβ) is initiating event, accelerating tau in entorhinal cortex (EC), which subsequently spreads into neocortex. Here a sample over 1300 participants with multimodal imaging and genetic information we queried how variation affects these stages cascade. We observed females APOE-ε4 homozygotes are more susceptible to effects Aβ on primary tau, greater EC for given level Aβ. Furthermore, individuals who have rare risk variants Triggering Receptor Expressed Myeloid Cells 2 (TREM2) and/or there was spread from These findings offer insights function sex, APOE microglia progression, implications determining personalised treatment drugs targeting tau.

Язык: Английский

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