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Blood-brain barrier and innate immunity in the pathogenesis of Alzheimer's disease


Šimić, Goran; Španić, Ena; Langer Horvat, Lea; Hof, Patrick R.
Blood-brain barrier and innate immunity in the pathogenesis of Alzheimer's disease // Progress in Molecular Biology and Translational Science, 168 (2019), 99-145 doi:10.1016/bs.pmbts.2019.06.003 (međunarodna recenzija, članak, znanstveni)


Naslov
Blood-brain barrier and innate immunity in the pathogenesis of Alzheimer's disease

Autori
Šimić, Goran ; Španić, Ena ; Langer Horvat, Lea ; Hof, Patrick R.

Izvornik
Progress in Molecular Biology and Translational Science (1877-1173) 168 (2019); 99-145

Vrsta, podvrsta i kategorija rada
Radovi u časopisima, članak, znanstveni

Ključne riječi
Alzheimer's disease ; Amyloid β ; Astrocytes ; Blood-brain barrier ; Cerebrospinal fluid ; Innate immunity ; Microglia ; Monocytes ; Neuroinflammation ; Tau proteins

Sažetak
The pathogenesis of Alzheimer's disease (AD) is only partly understood. This is the probable reason why significant efforts to treat or prevent AD have been unsuccessful. In fact, as of April 2019, there have been 2094 studies registered for AD on the clinicaltrials.gov U.S. National Library of Science web page, of which only a few are still ongoing. In AD, abnormal accumulation of amyloid and tau proteins in the brain are thought to begin 10-20 years before the onset of overt symptoms, suggesting that interventions designed to prevent pathological amyloid and tau accumulation may be more effective than attempting to reverse a pathology once it is established. However, to be successful, such early interventions need to be selectively administered to individuals who will likely develop the disease long before the symptoms occur. Therefore, it is critical to identify early biomarkers that are strongly predictive of AD. Currently, patients are diagnosed on the basis of a variety of clinical scales, neuropsychological tests, imaging and laboratory modalities, but definitive diagnosis can be made only by postmortem assessment of underlying neuropathology. People suffering from AD thus may be misdiagnosed clinically with other primary causes of dementia, and vice versa, thereby also reducing the power of clinical trials. The amyloid cascade hypothesis fits well for the familial cases of AD with known mutations, but is not sufficient to explain sporadic, late-onset AD (LOAD) that accounts for over 95% of all cases. Since the earliest descriptions of AD there have been neuropathological features described other than amyloid plaques (AP) and neurofibrillary tangles (NFT), most notably gliosis and neuroinflammation. However, it is only recently that genetic and experimental studies have implicated microglial dysfunction as a causal factor for AD, as opposed to a merely biological response of its accumulation around AP. Additionally, many studies have suggested the importance of changes in blood-brain barrier (BBB) permeability in the pathogenesis of AD. Here we suggest how these less investigated aspects of the disease that have gained increased attention in recent years may contribute mechanistically to the development of lesions and symptoms of AD.

Izvorni jezik
Engleski

Znanstvena područja
Biologija, Temeljne medicinske znanosti, Kliničke medicinske znanosti



POVEZANOST RADA


Projekt / tema
HRZZ-IP-2014-09-9730 - Hiperfosforilacija, agregacija i transsinaptički prijenos tau proteina u Alzheimerovoj bolesti: analiza likvora i ispitivanje potencijalnih neuroprotektivnih spojeva

Ustanove
Medicinski fakultet, Zagreb

Profili:

Avatar Url Ena Španić (autor)

Avatar Url Goran Šimić (autor)

Avatar Url Lea Langer Horvat (autor)

Citiraj ovu publikaciju

Šimić, Goran; Španić, Ena; Langer Horvat, Lea; Hof, Patrick R.
Blood-brain barrier and innate immunity in the pathogenesis of Alzheimer's disease // Progress in Molecular Biology and Translational Science, 168 (2019), 99-145 doi:10.1016/bs.pmbts.2019.06.003 (međunarodna recenzija, članak, znanstveni)
Šimić, G., Španić, E., Langer Horvat, L. & Hof, P. (2019) Blood-brain barrier and innate immunity in the pathogenesis of Alzheimer's disease. Progress in Molecular Biology and Translational Science, 168, 99-145 doi:10.1016/bs.pmbts.2019.06.003.
@article{article, year = {2019}, pages = {99-145}, DOI = {10.1016/bs.pmbts.2019.06.003}, keywords = {Alzheimer's disease, Amyloid β, Astrocytes, Blood-brain barrier, Cerebrospinal fluid, Innate immunity, Microglia, Monocytes, Neuroinflammation, Tau proteins}, journal = {Progress in Molecular Biology and Translational Science}, doi = {10.1016/bs.pmbts.2019.06.003}, volume = {168}, issn = {1877-1173}, title = {Blood-brain barrier and innate immunity in the pathogenesis of Alzheimer's disease}, keyword = {Alzheimer's disease, Amyloid β, Astrocytes, Blood-brain barrier, Cerebrospinal fluid, Innate immunity, Microglia, Monocytes, Neuroinflammation, Tau proteins} }

Časopis indeksira:


  • Web of Science Core Collection (WoSCC)
    • Science Citation Index Expanded (SCI-EXP)
    • SCI-EXP, SSCI i/ili A&HCI
  • Scopus
  • MEDLINE


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