ROLUL HOMOCISTEINEI ÎN PATOGENIA BOLII ALZHEIMER

Abstract

Introducere. Homocisteina (HC) este un aminoacid intermediar al metabolismului metioninei, strâns dependent de vitamina B12. În condiţii patologice, nivelurile plasmatice ale HC cresc, determinând apariţia hiperhomocisteine-miei (hHC) - implicată în patogeneza maladiilor neurode-generative, precum boala Alzheimer (BA). Scop. Stabilirea mecanismelor patofiziologice cheie prin care hiperhomo-cisteinemia contribuie la dezvoltarea şi progresia BA. Aprecierea potenţialului terapeutic al suplimentării cu vitamina B12. Material şi metode. Revista literaturii, bazată pe criteriile PRISMA, include 17 studii - 3 meta-analize, 8 revizuiri narative, 4 observaţionale, 2 experimentale. Au fost selectate articole (art) publicate între 2016-2025 în bazele de date PubMed şi ScienceDirect folosind termenii cheie: „Hy-per-/homocysteine”; „Neurodegeneration”; „Alzheimer’s disease”; „vitamin B12”. Rezultate. Studiile susţin rolul HC în patofiziologia BA, implicând-o în: acumularea amiloidu-lui-p (AP); hiperfosforilarea proteinelor tau (p-tau); stresul oxidativ; disfuncţia sinaptică. hHC accelerează proteinopa-tia: Ap - via hipometilarea ADN şi activarea y-secretazelor (4 art); p-tau - prin activarea GSK3 şi caspazei-3 (3 art). Idem, hHC induce stres oxidativ (auto-oxidarea HC, neuroin-flamaţie, disfuncţie endotelială, -7 art) şi excitotoxicitate (agonist AMPAR şi NMDAR, inhibitor GABA-A/B, -3 art). Vi-tamino-terapia B12 s-a asociat cu reducerea nivelurilor HC serică, susţinerea funcţiei colinergice şi ameliorarea performanţei cognitive (4 art). Concluzii. Hiperhomocisteinemia contribuie prin multiple mecanisme patofiziologice la procesul neurodegenerativ specific bolii Alzheimer. Suplimentarea cu vitamina B12 reprezintă o opţiune promiţătoare în reducerea impactului patologic al homocisteinei şi susţinerea funcţiei cognitive.

Introduction. Homocysteine (HC) is an intermediary amino-acid of methionine metabolism, which is tightly regulated by vitamin B12. In pathological conditions, plasma levels of HC increase, leading to hyperhomocysteinemia (hHC) - involved in the pathogenesis of neurodegenerative diseases, such as Alzheimer’s Disease (AD). Objective. To establish the key pathophysiologic mechanisms by which hyperhomocysteinemia contributes to the development and progression of AD. To assess the therapeutic potential of vitamin B12 supplementation. Material and methods. The narrative review, done according to PRISMA, includes 17 studies (3 meta-analysis, 8 narrative reviews, 4 observational, 2 experimental). Articles (art) published between 2016-2025 were selected from the data bases PubMed and ScienceDirect, using the key-words: „Hyper-/homocyste-ine”; „Neurodegeneration”; „Alzheimer’s disease”; „vitamin B12”. Results. Studies support HC’s role in AD’s pathophysiology, tying it to: accumulation of p-amyloids (PA); tau protein hyperphosphorylation (tau-p); oxidative stress; synaptic dysfunction. hHC accelerates the proteinopathy: PA - via DNA hypomethylation and y -secretase activation (4 art); tau-p - by GSK3 and caspase-3 activation (3 art). Also, hHC induces oxidative stress (HC auto-oxidation, neuroinflammation, endothelial dysfunction, -7 art) and excitotoxicity (AMPAR and NMDAR agonist, GABA-A/B inhibitor, - 3 art). Vitamin B12 therapy was related to dropping HC plasma levels, cholinergic function support and cognitive performance improvement (4 art). Conclusion. Hyperhomocysteinemia contributes to the specific neurodegenerative process of Alzheimer’s Disease through multiple pathophysiological mechanisms. Vitamin B12 supplementation represents a promising option in reducing the pathological impact of homocysteine and cognitive function support.