mTOR in a mouse model of Alzheimer's disease with cerebral amyloid angiopathy
In Tg2576 mice, an Alzheimer's model with cerebral amyloid angiopathy, mTOR drove accumulation of fibrillar vascular amyloid β, blood-brain barrier breakdown and impaired cerebrovascular and neurovascular function; the mTOR inhibitor rapamycin improved contextual memory in these mice. [1]
Automatic summary · not editorially reviewed
The key findings
In the Tg2576 mouse model of Alzheimer's disease with cerebral amyloid angiopathy, mTOR drove accumulation of fibrillar vascular amyloid β lesions, which directly impaired endothelium-dependent cerebrovascular reactivity. [1]
mTOR-dependent blood-brain barrier breakdown and tight junction remodeling were associated with increased cerebral microhemorrhages, and mTOR contributed to neurovascular uncoupling through nNOS dysfunction. [1]
The mTOR inhibitor rapamycin ameliorated contextual memory impairments in these mice, and the authors call mTOR inhibitors a promising treatment option for patients with CAA and Alzheimer's disease. [1]
The source at a glance
- Study type / format
- Preclinical study in a mouse model (abstract)
- Population / context
- Tg2576 mice, a model of Alzheimer's disease with cerebral amyloid angiopathy, with equal numbers of female and male mice.
- Summary based on
- Study abstract
- Publication status
- Preprint · peer-review status not confirmed
- Original publication
- June 28, 2026
mTOR and vascular amyloid in Tg2576 mice
The abstract describes cerebral amyloid angiopathy (CAA) as deposition of amyloid β fibrils in the walls of brain blood vessels, linked to brain hemorrhage, ischemic stroke and cognitive problems in Alzheimer's disease and in non-pathological aging. The authors report that mTOR drove accumulation of fibrillar vascular amyloid β lesions in the Tg2576 mouse model of Alzheimer's disease with CAA, using equal numbers of female and male mice. These lesions directly impaired endothelium-dependent cerebrovascular reactivity, meaning the vessels' response that depends on the inner vessel lining.
Supporting source [1]
Blood-brain barrier and neurovascular coupling findings
The abstract states that blood-brain barrier breakdown and remodeling of tight junction proteins, dependent on mTOR, were associated with increased cerebral microhemorrhages. It also reports that mTOR contributed to neurovascular uncoupling in Tg2576 mice through nNOS dysfunction and inhibition of non-nitric oxide synthase-dependent contributions to neurovascular coupling. Neurovascular coupling links brain activity to local blood flow.
Supporting source [1]
Rapamycin and memory in this mouse model
Contextual memory impairments were ameliorated by the mTOR inhibitor rapamycin. The abstract says these memory improvements were associated with reduced cerebrovascular amyloid β fibril accumulation, enhanced endothelium-dependent vasodilation, reduced fibrillar amyloid β load, restoration of blood-brain barrier integrity, attenuation of intracerebral microhemorrhage and restoration of neurovascular coupling. The authors conclude that mTOR inhibitors represent a promising treatment option for patients with CAA and Alzheimer's disease.
Supporting source [1]
How to interpret this
This is an abstract; the full text was not reviewed. All findings come from the Tg2576 mouse model of Alzheimer's disease with cerebral amyloid angiopathy, not from patients. The described associations and the rapamycin effects are preclinical; the statement that mTOR inhibitors are a promising treatment option is the authors' outlook, not evidence of benefit in people.
Based on the study abstract; the full paper, tables and supplementary data were not reviewed.
Source & supporting passages
Van Skike CE, Miller LR, Hernandez SF, Hussong SA, Makhlouf H, Muppala AC, DeRosa N, Jahrling JB, Dineley KT, Galvan V. · europepmc.org · June 28, 2026