Does Alzheimer's disease with mesial temporal lobe epilepsy represent a distinct disease subtype?
Alzheimer's disease (AD)
cognition
dementia
epilepsy
mild cognitive impairment (MCI)
seizures
tau
temporal lobe epilepsy
Journal
Alzheimer's & dementia : the journal of the Alzheimer's Association
ISSN: 1552-5279
Titre abrégé: Alzheimers Dement
Pays: United States
ID NLM: 101231978
Informations de publication
Date de publication:
06 2023
06 2023
Historique:
revised:
19
12
2022
received:
27
09
2022
accepted:
21
12
2022
pmc-release:
01
06
2024
medline:
13
6
2023
pubmed:
18
1
2023
entrez:
17
1
2023
Statut:
ppublish
Résumé
Alzheimer's disease (AD) patients have a high risk of developing mesial temporal lobe epilepsy (MTLE) and subclinical epileptiform activity. MTLE in AD worsens outcomes. Therefore, we need to understand the overlap between these disease processes. We hypothesize that AD with MTLE represents a distinct subtype of AD, with the interplay between tau and epileptiform activity at its core. We discuss shared pathological features including histopathology, an initial mesial temporal lobe (MTL) hyperexcitability followed by MTL dysfunction and involvement of same networks in memory (AD) and seizures (MTLE). We provide evidence that tau accumulation linearly increases neuronal hyperexcitability, neuronal hyper-excitability increases tau secretion, tau can provoke seizures, and tau reduction protects against seizures. We speculate that AD genetic mutations increase tau, which causes proportionate neuronal loss and/or hyperexcitability, leading to seizures. We discuss that tau burden in MTLE predicts cognitive deficits among (1) AD and (2) MTLE without AD. Finally, we explore the possibility that anti-seizure medications improve cognition by reducing neuronal hyper-excitability, which reduces seizures and tau accumulation and spread. HIGHLIGHTS: We hypothesize that patients with Alzheimer's disease (AD) and mesial temporal lobe epilepsy (MTLE) represents a distinct subtype of AD. AD and MTLE share histopathological features and involve overlapping neuronal and cortical networks. Hyper-phosphorylated tau (pTau) increases neuronal excitability and provoke seizures, neuronal excitability increases pTau, and pTau reduction reduces neuronal excitability and protects against seizures. The pTau burden in MTL predicts cognitive deficits among (1) AD and (2) MTLE without AD. We speculate that anti-seizure medications improve cognition by reducing neuronal excitability, which reduces seizures and pTau.
Identifiants
pubmed: 36648207
doi: 10.1002/alz.12943
pmc: PMC10272023
mid: NIHMS1861878
doi:
Types de publication
Journal Article
Research Support, Non-U.S. Gov't
Research Support, N.I.H., Extramural
Langues
eng
Sous-ensembles de citation
IM
Pagination
2697-2706Subventions
Organisme : NINDS NIH HHS
ID : U24 NS107182
Pays : United States
Commentaires et corrections
Type : CommentIn
Informations de copyright
© 2023 The Authors. Alzheimer's & Dementia published by Wiley Periodicals LLC on behalf of Alzheimer's Association.
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