Proteomic Atlas of the Human Brain in Alzheimer’s Disease

The
brain represents one of the most divergent and critical organs
in the human body. Yet, it can be afflicted by a variety of neurodegenerative
diseases specifically linked to aging, about which we lack a full
biomolecular understanding of onset and progression, such as Alzheimer’s
disease (AD). Here we provide a proteomic resource comprising nine
anatomically distinct sections from three aged individuals, across
a spectrum of disease progression, categorized by quantity of neurofibrillary
tangles. Using state-of-the-art mass spectrometry, we identify a core
brain proteome that exhibits only small variance in expression, accompanied
by a group of proteins that are highly differentially expressed in
individual sections and broader regions. AD affected tissue exhibited
slightly elevated levels of tau protein with similar relative expression
to factors associated with the AD pathology. Substantial differences
were identified between previous proteomic studies of mature adult
brains and our aged cohort. Our findings suggest considerable value
in examining specifically the brain proteome of aged human populations
from a multiregional perspective. This resource can serve as a guide,
as well as a point of reference for how specific regions of the brain
are affected by aging and neurodegeneration.