Accumulation of amyloid beta-protein in the low-density membrane domain accurately reflects the extent of beta-amyloid deposition in the brain

To learn more about the process of amyloid beta -protein (A beta) depositio n in the brain, human prefrontal cortices were fractionated by sucrose dens ity gradient centrifugation, and the A beta content in each fraction was qu antified by a two-site enzyme-linked immunosorbent assay. The fractionation protocol revealed two pools of insoluble A beta. One corresponded to a low -density membrane domain; the other was primarily composed of extracellular A beta deposits in those cases in which A beta accumulated to significant levels. A beta 42 levels in the low-density membrane domain were proportion al to the extent of total A beta 42 accumulation, which is known to correla te well with overall amyloid burden. In PDAPP mice that form senile plaques and accumulate A beta in a similar manner to aging humans, A beta 42 accum ulation in the low-density membrane domain also increased as A beta deposit ion progressed with aging. These observations indicate that the A beta 42 a ssociated with low-density membrane domains is tightly coupled with the pro cess of extracellular A beta deposition.