Soluble Conformers of Aβ and Tau Alter Selective Proteins Governing Axonal Transport.
Mathew A ShermanMichael LaCroixFatou AmarMegan E LarsonColleen L ForsterAdriano AguzziDavid A BennettMartin RamsdenSylvain E LesnéPublished in: The Journal of neuroscience : the official journal of the Society for Neuroscience (2017)
The mechanistic link between amyloid-β (Aβ) and tau, the two major proteins composing the neuropathological lesions detected in brain tissue of Alzheimer's disease subjects, remains unclear. Here, we report that the trimeric Aβ species induce a pathological modification of tau in cultured neurons and in bigenic mice expressing Aβ and human tau. This linkage was also observed in postmortem brain tissue from subjects with mild cognitive impairment, when Aβ trimers are abundant. Further, this modification of tau was associated with the intracellular accumulation of the precursor protein of Aβ, APP, as a result of the selective decrease in kinesin light chain 1 expression. Our findings suggest that Aβ trimers might cause axonal transport deficits in AD.
Keyphrases
- mild cognitive impairment
- cerebrospinal fluid
- cognitive decline
- endothelial cells
- spinal cord injury
- resting state
- poor prognosis
- white matter
- traumatic brain injury
- spinal cord
- type diabetes
- gene expression
- multiple sclerosis
- genome wide
- skeletal muscle
- adipose tissue
- functional connectivity
- human immunodeficiency virus
- insulin resistance
- hepatitis c virus
- metabolic syndrome
- hiv testing
- antiretroviral therapy
- men who have sex with men
- hiv infected
- genetic diversity