What is pathophysiology of Alzheimer?

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Što je patofiziologija Alzheimera?

Patofiziologija Alzheimerove bolesti (AD) je složen proces koji uključuje akumulaciju abnormalnih proteina, upalu i neuronsku disfunkciju.

Dvije glavne karakteristike AD-a su prisutnost amiloid-beta (Aβ) plakova i neurofibrilarnih zamaka (NFT-ovi) u mozgu.

Amyloid- beta plake nastaju kada se fragmenti amiloidnog prekursorskog proteina (APP) razdvajaju enzimima kako bi se formirali Aβ peptidi.

Ovi se peptidi skupljaju i formiraju nerastvorljive fibrile koje se akumuliraju izvan neurona, narušavajući komunikaciju između stanica i dovodeći do smrti neurona.

Smatra se da je akumulacija Aβ plakova jedan od najranijih događaja u razvoju AD- a, i vjeruje se da doprinosi neurodegenerativnom procesu.

Neurofibrilarne zamke nastaju kada protein tau postane hiperfosforiliran i formira abnormalne filamente unutar neurona.

Ove zamke ometaju normalno funkcioniranje mikrotubula, koji su od suštinskog značaja za transport hranjivih tvari i drugih materijala unutar neurona.

Te zamke na kraju dovode do smrti zahvaćenih neurona.

Upala također igra ulogu u patofiziologiji AD-a.

Imunološki sustav reagira na akumulaciju Aβ plakova i NFT- a oslobađanjem proinflamatornih citokina, što može pogoršati oštećenje neurona.

Osim toga, postoje dokazi da oksidativni stres, mitohondrijska disfunkcija i oštećenje metabolizma glukoze doprinose patofiziologiji AD-a.

Ovi čimbenici mogu dovesti do disfunkcije i smrti neurona, što dodatno pogoršava proces bolesti.

Sve u svemu, patofiziologija AD-a je složena interakcija višestrukih čimbenika koji na kraju dovode do progresivnog opadanja kognitivne funkcije i gubitka pamćenja koji karakteriše bolest.

Referencije

PubMed/Medline https://www.nlm.nih.gov/databases/download/pubmed_medline.html

RefinedWeb https://arxiv.org/abs/2306.01116

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Candore G, Bulati M, Caruso C, Castiglia L, Colonna-Romano G, Di Bona D, Duro G, Lio D, Matranga D, Pellicanò M, Rizzo C, Scapagnini G, Vasto S: Inflammation, cytokines, immune response, apolipoprotein E, cholesterol, and oxidative stress in Alzheimer disease: therapeutic implications. Rejuvenation Res. , 13 (2-3): 301-13.

Raskind MA, Peskind ER: Neurobiologic bases of noncognitive behavioral problems in Alzheimer disease. Alzheimer Dis Assoc Disord. 1994, 8 Suppl 3 (): 54-60.

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What is pathophysiology of alzheimer?

The pathophysiology of Alzheimer's disease (AD) is a complex process that involves the accumulation of abnormal proteins, inflammation, and neuronal dysfunction.

The two main hallmarks of AD are the presence of amyloid-beta (Aβ) plaques and neurofibrillary tangles (NFTs) in the brain.

Amyloid-beta plaques are formed when fragments of the amyloid precursor protein (APP) are cleaved by enzymes to form Aβ peptides.

These peptides aggregate and form insoluble fibrils that accumulate outside neurons, disrupting cell-to-cell communication and leading to neuronal death.

The accumulation of Aβ plaques is thought to be one of the earliest events in the development of AD, and it is believed to contribute to the neurodegenerative process.

Neurofibrillary tangles are formed when the protein tau becomes hyperphosphorylated and forms abnormal filaments inside neurons.

These tangles disrupt the normal functioning of the microtubules, which are essential for the transport of nutrients and other materials within the neuron.

The tangles eventually lead to the death of the affected neurons.

Inflammation also plays a role in the pathophysiology of AD.

The immune system responds to the accumulation of Aβ plaques and NFTs by releasing pro-inflammatory cytokines, which can exacerbate the damage to neurons.

Additionally, there is evidence that oxidative stress, mitochondrial dysfunction, and impaired glucose metabolism contribute to the pathophysiology of AD.

These factors can lead to neuronal dysfunction and death, further exacerbating the disease process.

Overall, the pathophysiology of AD is a complex interplay of multiple factors that ultimately lead to the progressive decline in cognitive function and memory loss that characterizes the disease.

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