Naslov
Biomarkeri Alzheimerove bolesti
(Alzheimer's disease biomarkers)

Autori
Španić Popovački, Ena ; Šimić, Goran

Vrsta, podvrsta i kategorija rada
Sažeci sa skupova, sažetak, stručni

Izvornik
Alzheimer Akademija / Klepac, N ; Borovečki, F - Zagreb, 2023, 1-1

Skup
Alzheimer's disease Academy with international participation

Mjesto i datum
Zagreb, Hrvatska, 03.02.2023. - 04.02.2023

Vrsta sudjelovanja
Pozvano predavanje

Vrsta recenzije
Domaća recenzija

Ključne riječi
Alzheimer's disease ; biomarkers ; cerebrospinal fluid ; exosomes

Sažetak
The neuropathologic hallmarks of Alzheimer's disease (AD) include the following key features: amyloid plaques, neurofibrillary tangles (NFTs ; composed of abnormally phosphorylated tau proteins), glial responses, and synaptic and neuronal loss. Across the AD continuum, Aβ plaques are thought to be the earliest pathological changes that are followed by tau NFTs accumulation, inflammation, synaptic degeneration, and neuronal loss. Neurodegeneration and synapse loss are the best correlates of clinical symptoms. Around 20% of the peptides and proteins in CSF are derived from the brain. The concentration of brain-derived peptides and proteins is the highest in the ventricles and decreases as it flows to the subarachnoid spaces. Blood testing is less invasive than CSF testing and can easily be performed in a variety of settings and at repeated intervals. Blood-based biomarkers, reflecting proteins originating from the brain, are typically present at low concentrations because of dilution in the volume of blood ; biomarkers present in the blood may also undergo additional proteolytic cleavage by proteases in plasma. CSF total tau protein (t-tau) measures the intensity of neurodegeneration in AD but is not a disease-specific marker. T-tau is increased in the CSF of patients with AD dementia and some other neurological conditions whereas phosphorylated tau (p-tau) in CSF measures the amount of tau that is phosphorylated, a variant of tau found in NFTs. In AD, p-tau in CSF is increased. On the other hand, CSF amyloid (Aβ42) is decreased in AD and is thought to reflect the aggregation and deposition of the protein in the brain. Neuronal/astrocyte-derived exosomes in AD have increased content of Aβ42, p-tau181, p-tau396, t-tau, BACE-1, APP, complement effector proteins, IL1β, IL-6, TNF-α, cathepsin D, LAMP-1, ubiquitinylated proteins, AACT, RAS suppressor protein, GP1B, whereas the content of neurogranin, neuromodulin, SNAP-25, synaptotagmin, synaptopodin, synaptophysin, complement regulatory proteins, neurotrophic and growth factors is decreased. Plasma brain-derived exosomes, either neuronal or astrocytic, have multiple potential roles. Harmful actions include the spreading of amyloid and tau pathological changes, mediating neuron-to-neuron propagation of both amyloid and tau oligomers, and induction of neuronal apoptotic pathways. Beneficial actions include binding of extracellular Aβ42 and promoting its degradation, neutralizing Aβ-induced disruption in synaptic plasticity, carrying nucleic acids with gene expression regulating abilities, and serving as therapeutic vehicles of drug delivery for AD. The current inconsistency between the extraction of exosomes and detection procedures of exosome cargos is one of the main limitations of exosome-related studies.

Izvorni jezik
Engleski

Znanstvena područja
Biologija, Temeljne medicinske znanosti, Kliničke medicinske znanosti, Psihologija, Kognitivna znanost (prirodne, tehničke, biomedicina i zdravstvo, društvene i humanističke znanosti)

POVEZANOST RADA