In vivo conversion of racemized β‐amyloid ([D‐Ser²⁶]Aβ1–40) to truncated and toxic fragments ([D‐Ser²⁶]Aβ25–35/40) and fragment presence in the brains of Alzheimer's patients

Abstract

The lag between ␤-amyloid (A␤) deposition and neurodegeneration in Alzheimer's disease (AD) suggests that age-dependent factors are involved in the pathogenesis.

Time-Course and Regional Analyses of the Physiopathological Changes Induced after Cerebral Injection of an Amyloid β Fragment in Rats

“…This short fragment has been identified in AD patient brains and is likely produced endogenously by enzymatic cleavage of A␤ . 15,32 Indeed, findings from the IHC study of Kubo et al 15 support the idea that Figure 10. A: Variations in GFAP levels in the frontal cortex, amygdala, hippocampus, and hypothalamus determined in rats by Western blotting at 1, 2, and 3 weeks after injection of scrambled A␤ [25][26][27][28][29][30][31][32][33][34][35] peptide (10 g/rat i.c.v., negative control) or A␤ 25-35 (10 g/rat i.c.v.).…”

“…15 Deposits of A␤ [25][26][27][28][29][30][31][32][33][34][35] peptide after its injection have not yet been characterized by IHC, for lack of specific and selective antibodies. However, Klementiev et al 16 and Chavant et al 17 reported an accumulation of A␤ immunolabeling in the hippocampus and cerebral cortex, induced 4 and 2 weeks, respectively, after the A␤ [25][26][27][28][29][30][31][32][33][34][35] injection.…”

“…The grounds for objection center on three points. First, although the presence of A␤ [25][26][27][28][29][30][31][32][33][34][35] has been repeatedly demonstrated in brains of AD patients, 14,15 this fragment appears to be a minor peptide in plaques and its contribution to the toxicity induced by all amyloid-related species remains unclear. Second, the intracerebroventricular injection of A␤ [25][26][27][28][29][30][31][32][33][34][35] induces marked toxicity within days or weeks, which is not in accord with the long-term progression of AD in humans (an argument that is unrelated to the nature of the toxicity).…”

Minocycline provides protection against β-amyloid(25-35)-induced alterations of the somatostatin signaling pathway in the rat temporal cortex

“…In the past, the presence of A␤(25-35) in vivo was controversial. Kubo et al (2002) revealed the presence of both fragments in the AD brain but not in age-matched control brains (Kubo et al, 2002).…”

Somatostatin and Alzheimer's disease

“…For many years, the presence of this 11-aminoacid fragment in vivo was questioned. In 2002, Kubo et al provided (Kubo et al, 2002). An accumulation of Aβ peptides has been associated with progressive neuronal death, cognitive deficits and neuropsychiatric disorders such as agitation, apathy and increased…”