An experimental model of Braak's pretangle proposal for the origin of Alzheimer's disease: the role of locus coeruleus in early symptom development.
Abhinaba GhoshSarah E TorravilleBandhan MukherjeeSusan G WallingGerard M MartinCarolyn W HarleyQi YuanPublished in: Alzheimer's research & therapy (2019)
Our animal model suggests, for the first time, that Braak's hypothesis that human AD originates with pretangle stages is plausible. LC pretangle progression here generates both preclinical AD pathological changes and cognitive decline. The odor discrimination deficits are similar to human odor identification deficits seen with aging and preclinical AD. When initiated in aged rats, pretangle stages progress rapidly and cause LC cell loss. These age-related outcomes are associated with a severe learning impairment consistent with memory decline in Braak stages III-IV.
Keyphrases
- cognitive decline
- endothelial cells
- mild cognitive impairment
- cell therapy
- traumatic brain injury
- induced pluripotent stem cells
- pluripotent stem cells
- mass spectrometry
- simultaneous determination
- single cell
- stem cells
- metabolic syndrome
- working memory
- high resolution
- solid phase extraction
- patient reported
- gas chromatography