APP/Aβ Signaling Orchestrates Reactive Astrocyte Networks in Alzheimer's Disease

Velezmoro Jauregui, Gretsen (avtor), Zorec, Robert (avtor), Stokin, Gorazd Bernard (avtor)

Alzheimer's disease (AD) is characterized by amyloid-β (Aβ) accumulation, neurofibrillary pathology, synaptic dysfunction, and chronic neuroinflammation, yet the mechanisms driving early, localized pathology remain elusive. While traditionally viewed through a neuron-centric lens, astrocytes express abundant amyloid precursor protein (APP)-predominantly Kunitz-type protease inhibitor (KPI)-containing isoforms-and possess the complete enzymatic machinery for APP processing and Aβ clearance. Astrocytic APP is a stress-responsive signaling molecule regulated by inflammatory, metabolic, excitotoxic, and mechanical insults. Under local tissue stress, reactive astrocytes upregulate APP and shift toward amyloidogenic processing. The resulting bioactive fragments, including Aβ, promote astrocyte activation, disrupt homeostatic functions, and trigger feed-forward upregulation of endogenous APP. We propose that this reciprocal coupling establishes a self-reinforcing network where APP integrates local stress and diffusible Aβ propagates reactive states across the astroglial syncytium. This framework positions astrocytic APP signaling as an upstream driver of localized amyloid accumulation, neuroinflammation, and sporadic AD progression.

• Jezik: Angleški jezik
• Ključne besede: Alzheimer's disease, amyloid precursor protein, amyloid‐β peptides, reactive astrocytes
• Vrsta gradiva: Članek v reviji
• Tipologija: 1.02 - Pregledni znanstveni članek
• Organizacija: MF - Medicinska fakulteta
• Status publikacije: Objavljeno
• Različica publikacije: Objavljena publikacija
• Leto izida: 2026
• Št. strani: 19 str.
• Številčenje: Vol. 170, iss. 7, art. e70526
• PID: 20.500.12556/RUL-185774
• UDK: 616.8
• ISSN pri članku: 1471-4159
• DOI: 10.1111/jnc.70526
• COBISS.SI-ID: 287894275
• Datum objave v RUL: 20.08.2026

Gradivo je del revije

• Naslov: Journal of neurochemistry
• Skrajšan naslov: J. neurochem.
• Založnik: Wiley, International Society for Neurochemistry
• ISSN: 1471-4159
• COBISS.SI-ID: 515029529

Licence

• Licenca: CC BY 4.0, Creative Commons Priznanje avtorstva 4.0 Mednarodna
• Povezava: http://creativecommons.org/licenses/by/4.0/deed.sl
• Opis: To je standardna licenca Creative Commons, ki daje uporabnikom največ možnosti za nadaljnjo uporabo dela, pri čemer morajo navesti avtorja.

Sekundarni jezik

• Jezik: Slovenski jezik
• Ključne besede: Alzheimerjeva bolezen, amiloidni prekurzorski protein, amiloid-β peptidi, reaktivni astrociti