Cerebral Phospho-Tau Acts Synergistically with Soluble Aß42 Leading to Mild Cognitive Impairment in AAV-AD Rats.
J Prev Alzheimers Dis
; 9(3): 480-490, 2022.
Article
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| MEDLINE
| ID: mdl-35841249
ABSTRACT
BACKGROUND:
Alzheimer's disease (AD) is a continuum of events beginning with an increase in brain soluble Aß42 followed by the appearance of hyperphosphorylated tau (P-tau, asymptomatic stage). Mild Cognitive Impairment (MCI) then appears (prodromal stage). However, the individual contribution of these two soluble proteins in the onset of the first cognitive symptoms remains unclear.OBJECTIVES:
We sought to understand the specific impact of p-tau on the development of MCI in the AAV-AD rat model, a model of late-onset Alzheimer's disease (LOAD) predementia.METHODS:
We specifically reduced the phosphorylation level of tau while leaving Aß42 levels unchanged using a DYRK1A protein kinase inhibitor, Leucettine L41, in an adeno-associated virus-based Alzheimer's disease (AAV-AD) rat model. Leucettine L41 was administered by intraperitoneal injection at 20 mg/kg per day in AAV-AD rats from 9 (late asymptomatic phase) to 10 (prodromal phase) months of age.RESULTS:
Decreased soluble forms of P-tau induced by chronic administration of Leucettine L41 did not change soluble Aß42 levels but prevented MCI onset in 10-month-old AAV-AD rats.CONCLUSIONS:
The present study argues that P-tau is required to induce the development of MCI. Consistent with our previous findings that soluble Aß42 is also required for MCI onset, the data obtained in the AAV-AD rat model confirm that the transition from the asymptomatic to the prodromal stage may be caused by the combined presence of both soluble brain forms of Aß42 and p-tau, suggesting that the development of MCI may be the consequence of their synergistic action.Palabras clave
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Base de datos:
MEDLINE
Asunto principal:
Enfermedad de Alzheimer
/
Disfunción Cognitiva
Tipo de estudio:
Diagnostic_studies
/
Prognostic_studies
Idioma:
En
Revista:
J Prev Alzheimers Dis
Año:
2022
Tipo del documento:
Article