Intracellular Amyloid-β in the Normal Rat Brain and Human Subjects and Its relevance for Alzheimer's Disease

• BACKGROUND: Amyloid-β (Aβ) is a normal product of neuronal activity, including that of the aggregation-prone Aβ42 variant that is thought to cause Alzheimer's disease (AD). Much knowledge about AD comes from studies of transgenic rodents expressing mutated human amyloid-β protein precursor (AβPP) to increase Aβ production or the Aβ42/40 ratio. Yet, little is known about the normal expression of Aβ42 in rodent brains.OBJECTIVE: To characterize the brain-wide expression of Aβ42 throughout the life span of outbred Wistar rats, and to relate these findings to brains of human subjects without neurological disease.METHODS: Aβ42 immunolabeling of 12 Wistar rat brains (3-18 months of age) and brain sections from six human subjects aged 20-88 years.RESULTS: In healthy Wistar rats, we find intracellular Aβ42 (iAβ42) in neurons throughout the brain at all ages, but levels vary greatly between brain regions. The highest levels are in neurons of entorhinal cortex layer II, alongside hippocampal neurons at the CA1/subiculum border. Concerning entorhinal cortex layer II, we find similarly high levels of iAβ42 in the human subjects.CONCLUSION: Expression of iAβ42 in healthy Wistar rats predominates in the same structures where iAβ accumulates and Aβ plaques initially form in the much used, Wistar based McGill-R-Thy1-APP rat model for AD. The difference between wild-type Wistar rats and these AD model rats, with respect to Aβ42, is therefore quantitative rather that qualitative. This, taken together with our human results, indicate that the McGill rat model in fact models the underlying wild-type neuronal population-specific vulnerability to Aβ42 accumulation.

Ämnesord

MEDICIN OCH HÄLSOVETENSKAP  -- Medicinska och farmaceutiska grundvetenskaper -- Neurovetenskaper (hsv//swe)

MEDICAL AND HEALTH SCIENCES  -- Basic Medicine -- Neurosciences (hsv//eng)

Nyckelord

Alzheimer's disease

animal model

disease onset

entorhinal cortex

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art (ämneskategori)

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