PMID- 36979840
OWN - NLM
STAT- PubMed-not-MEDLINE
LR  - 20230331
IS  - 2227-9059 (Print)
IS  - 2227-9059 (Electronic)
IS  - 2227-9059 (Linking)
VI  - 11
IP  - 3
DP  - 2023 Mar 11
TI  - Alzheimer's Disease from the Amyloidogenic Theory to the Puzzling Crossroads 
      between Vascular, Metabolic and Energetic Maladaptive Plasticity.
LID - 10.3390/biomedicines11030861 [doi]
LID - 861
AB  - Alzheimer's disease (AD) is a progressive and degenerative disease producing the 
      most common type of dementia worldwide. The main pathogenetic hypothesis in 
      recent decades has been the well-known amyloidogenic hypothesis based on the 
      involvement of two proteins in AD pathogenesis: amyloid beta (Abeta) and tau. Amyloid 
      deposition reported in all AD patients is nowadays considered an independent risk 
      factor for cognitive decline. Vascular damage and blood-brain barrier (BBB) 
      failure in AD is considered a pivotal mechanism for brain injury, with increased 
      deposition of both immunoglobulins and fibrin. Furthermore, BBB dysfunction could 
      be an early sign of cognitive decline and the early stages of clinical AD. 
      Vascular damage generates hypoperfusion and relative hypoxia in areas with high 
      energy demand. Long-term hypoxia and the accumulation within the brain parenchyma 
      of neurotoxic molecules could be seeds of a self-sustaining pathological 
      progression. Cellular dysfunction comprises all the elements of the neurovascular 
      unit (NVU) and neuronal loss, which could be the result of energy failure and 
      mitochondrial impairment. Brain glucose metabolism is compromised, showing a 
      specific region distribution. This energy deficit worsens throughout aging. Mild 
      cognitive impairment has been reported to be associated with a glucose deficit in 
      the entorhinal cortex and in the parietal lobes. The current aim is to understand 
      the complex interactions between amyloid beta (Abeta) and tau and elements of the BBB 
      and NVU in the brain. This new approach aimed at the study of metabolic 
      mechanisms and energy insufficiency due to mitochondrial impairment would allow 
      us to define therapies aimed at predicting and slowing down the progression of 
      AD.
FAU - Cerasuolo, Michele
AU  - Cerasuolo M
AD  - Department of Advanced Medical and Surgical Sciences, University of Campania 
      "Luigi Vanvitelli", 80138 Naples, Italy.
FAU - Papa, Michele
AU  - Papa M
AUID- ORCID: 0000-0002-6609-7453
AD  - Laboratory of Neuronal Networks Morphology and System Biology, Department of 
      Mental and Physical Health and Preventive Medicine, University of Campania "Luigi 
      Vanvitelli", 80138 Naples, Italy.
AD  - SYSBIO Centre of Systems Biology ISBE-IT, 20126 Milan, Italy.
FAU - Colangelo, Anna Maria
AU  - Colangelo AM
AUID- ORCID: 0000-0002-7971-4289
AD  - SYSBIO Centre of Systems Biology ISBE-IT, 20126 Milan, Italy.
AD  - Laboratory of Neuroscience "R. Levi-Montalcini", Department of Biotechnology and 
      Biosciences, NeuroMI Milan Center for Neuroscience, University of Milano-Bicocca, 
      20126 Milano, Italy.
FAU - Rizzo, Maria Rosaria
AU  - Rizzo MR
AUID- ORCID: 0000-0002-1023-4260
AD  - Department of Advanced Medical and Surgical Sciences, University of Campania 
      "Luigi Vanvitelli", 80138 Naples, Italy.
LA  - eng
GR  - Mnesys-Piano Nazionale di Ripresa e Resilienza, 2022/NextGenerationEU/
GR  - HORIZON-EIC-2022-PATHFINDEROPEN-01 : THOR/European commission/
GR  - FOE 2020 JRU ISBE-IT/Ministero Universita e Ricerca/
GR  - FOE 2019 JRU ISBE-IT/Ministero Universita e Ricerca/
GR  - PRIN 2017-2017XJ38A4_003/Ministero Universita e Ricerca/
PT  - Journal Article
PT  - Review
DEP - 20230311
PL  - Switzerland
TA  - Biomedicines
JT  - Biomedicines
JID - 101691304
PMC - PMC10045635
OTO - NOTNLM
OT  - Alzheimer's disease
OT  - blood-brain barrier
OT  - glia
OT  - neurovascular unit
OT  - reactive oxygen species (ROS)
COIS- The authors declare no conflict of interest.
EDAT- 2023/03/30 06:00
MHDA- 2023/03/30 06:01
PMCR- 2023/03/11
CRDT- 2023/03/29 01:21
PHST- 2023/02/25 00:00 [received]
PHST- 2023/03/06 00:00 [revised]
PHST- 2023/03/09 00:00 [accepted]
PHST- 2023/03/30 06:01 [medline]
PHST- 2023/03/29 01:21 [entrez]
PHST- 2023/03/30 06:00 [pubmed]
PHST- 2023/03/11 00:00 [pmc-release]
AID - biomedicines11030861 [pii]
AID - biomedicines-11-00861 [pii]
AID - 10.3390/biomedicines11030861 [doi]
PST - epublish
SO  - Biomedicines. 2023 Mar 11;11(3):861. doi: 10.3390/biomedicines11030861.