Title :

Pathological changes induced by Alzheimer's brain inoculation in amyloid-beta plaque-bearing mice.

Author(s) :

Lam, S. [Auteur]
Université Paris-Saclay
Institut de Biologie François JACOB [JACOB]
Hérard, A. S. [Auteur]
Université Paris-Saclay
Institut de Biologie François JACOB [JACOB]
Boluda, S. [Auteur]
CHU Pitié-Salpêtrière [AP-HP]
Petit, F. [Auteur]
Université Paris-Saclay
Institut de Biologie François JACOB [JACOB]
Eddarkaoui, Sabiha [Auteur]
Lille Neurosciences & Cognition (LilNCog) - U 1172
Cambon, K. [Auteur]
Université Paris-Saclay
Institut de Biologie François JACOB [JACOB]
Picq, J. L. [Auteur]
Université Paris-Saclay
Institut de Biologie François JACOB [JACOB]
Buee, Luc [Auteur]
Lille Neurosciences & Cognition (LilNCog) - U 1172
Duyckaerts, C. [Auteur]
CHU Pitié-Salpêtrière [AP-HP]
Haïk, S. [Auteur]
CHU Pitié-Salpêtrière [AP-HP]
Dhenain, M. [Auteur]
Université Paris-Saclay
Institut de Biologie François JACOB [JACOB]

Journal title :

Acta Neuropathol Commun

Volume number :

10

Pages :

112

Publication date :

2022-08-18

ISSN :

2051-5960

English keyword(s) :

Alzheimer's disease
Amyloid-beta
Memory
Microglia
Synapses
Tau
Transmission

HAL domain(s) :

Sciences du Vivant [q-bio]

English abstract : [en]

Alzheimer's disease (AD) is characterized by intracerebral accumulations of extracellular amyloid-β (Aβ) plaques and intracellular tau pathology that spread in the brain. Three types of tau lesions occur in the form of ...
Show more >Alzheimer's disease (AD) is characterized by intracerebral accumulations of extracellular amyloid-β (Aβ) plaques and intracellular tau pathology that spread in the brain. Three types of tau lesions occur in the form of neuropil threads, neurofibrillary tangles, and neuritic plaques i.e. tau aggregates within neurites surrounding Aβ deposits. The cascade of events linking these lesions and synaptic or memory impairments are still debated. Intracerebral infusion of human AD brain extracts in Aβ plaque-bearing mice that do not overexpress pathological tau proteins induces tau pathologies following heterotopic seeding of mouse tau protein. There is however little information regarding the downstream events including synaptic or cognitive repercussions of tau pathology induction in these models. In the present study, human AD brain extracts (ADbe) and control-brain extracts (Ctrlbe) were infused into the hippocampus of Aβ plaque-bearing APPswe/PS1dE9 mice. Memory, synaptic density, as well as Aβ plaque and tau aggregate loads, microgliosis, astrogliosis at the inoculation site and in connected regions (perirhinal/entorhinal cortex) were evaluated 4 and 8 months post-inoculation. ADbe inoculation produced the following effects: (i) memory deficit; (ii) increased Aβ plaque deposition in proximity to the inoculation site; (iii) tau pathology induction; (iv) appearance of neuropil threads and neurofibrillary tangles next to the inoculation site with a spreading to connected regions. Neuritic plaque pathology was detected in both ADbe- and Ctrlbe-inoculated animals but ADbe inoculation increased the severity close to and at distance of the inoculation site. (v) Finally, ADbe inoculation reduced synaptic density in the vicinity to the inoculation site and in connected regions as the perirhinal/entorhinal cortex. Synaptic impairments were correlated with increased severity of neuritic plaques but not to other tau lesions or Aβ lesions, suggesting that neuritic plaques are a culprit for synaptic loss. Synaptic density was also associated with microglial load.Show less >

Language :

Anglais

Audience :

Internationale

Popular science :

Non

Administrative institution(s) :

Université de Lille
Inserm
CHU Lille

Collections :

• Lille Neurosciences & Cognition (LilNCog) - U 1172

Research team(s) :

Alzheimer et Tauopathies

Submission date :

2024-01-16T00:54:34Z
2024-12-18T11:10:40Z