Prevention and Reduction of AD‐type Pathology in PDAPP Mice Immunized with Aβ_1–42

Abstract

In AD certain brain structures contain a pathological density of Aβ protein deposited into plaques. The effect of genetic mutations found in early onset AD patients was an overproduction of Aβ42, strongly suggesting that overproduction of Aβ42 is associated with AD. We hypothesized that an immunological response to Aβ42 might alter its turnover and metabolism. Young PDAPP transgenic mice were immunized with Aβ1–42, which essentially prevented amyloid deposition; astrocytosis was dramatically reduced and there was reduction in Aβ‐induced inflammatory response as well. Aβ1–42 immunization also appeared to arrest the progression of amyloidosis in older PDAPP mice. Aβ immunization appears to increase clearance of amyloid plaques, and may therefore be a novel and effective approach for the treatment of AD.

Complex Pharmacokinetics of a Humanized Antibody Against Human Amyloid Beta Peptide, Anti-Abeta Ab2, in Nonclinical Species

“…For the treatment of AD, both passive Aβ immunization (i.e. peripheral administration of anti-Aβ antibodies) and active immunization with Aβ are being explored (1)(2)(3)(4)(5). The amino acid sequence of Aβ 1-42 is 100% conserved between humans and most primates; however, the N-terminal Aβ sequence is not conserved between primates and rodents.…”

Transgenic animal models of Alzheimer's disease and related disorders: histopathology, behavior and therapy

“…190 Subsequently, other research groups confirmed the efficacy of the Ab immunization by various routes, including intranasal administration. 192,193 Further studies revealed that immunization also reduced age-dependent learning deficits. Vaccination with Ab protected APP/PS1 double transgenic mice from age-related memory deficits that normally occur in these mice: At an age when untreated transgenic mice showed memory deficits on the radial-arm water maze test of working memory, the Ab-vaccinated transgenic mice showed a cognitive performance that was superior to that of the control transgenic mice and, ultimately, performed as well as non-transgenic mice.…”

Therapeutic potential of oxidant mechanisms in Alzheimer’s disease

“…In their experiments with transgenic mice, they were be able to show that simple immunization with Aβ 1-42 can block the deposition of amyloid and clear the existing amyloid plaques in the brain of transgenic AβPP mice [50]. Indeed, studies in transgenic mice that overexpress an AD-causing mutant form of human AβPP and develop amyloid deposits have revealed that crossing such mice with mice overexpressing a natural inhibitor of complement C3 results in worsening of Aβ plaque load and more neuronal loss [49].…”