Journal
NEUROCHEMISTRY INTERNATIONAL
Volume 46, Issue 3, Pages 253-260Publisher
PERGAMON-ELSEVIER SCIENCE LTD
DOI: 10.1016/j.neuint.2004.08.006
Keywords
A beta PP; DLB; PD; amyloid angiopathy; AD; PSP
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Deposition of amyloid-beta, the fibrillogenic product of the cell surface protein APPP (amyloid-beta protein precursor), occurs in the cerebral cortex of patients with Dementia with Lewy bodies (DLB). Amyloid deposition, basically in the form of senile plaques, occurs not only in the common form (DLBc), which is defined by changes consistent with diffuse Lewy body disease accompanied by Alzheimer's disease (AD), but also in the pure form (DLBp), in which neurofibrillary tangles are absent. The present study analyses the expression of APPP mRNA isoforms with (AbetaPP751 and AbetaPP770) and without (AbetaPP695) the Kunitz-type serine protease inhibitor (KPI) domain, in the cerebral cortex in DLBc (n = 4), DLBp (n = 4), Parkinson's disease (PD, n = 5), AD (n = 3 stages I-IIA, and n = 4 stage VC of Braak and Braak), amyloid angiopathy (AA, n = 2) and progressive supranuclear palsy (PSP, n = 4) compared with age-matched controls (H = 6). For this purpose, TaqMan RT-PCR assay was used on frozen post-mortem samples of the frontal cortex (area 8) obtained with short post-mortem delays (8.29 +/- 4.57 h) and strict RNA preservation (A(260/280) Of 1.78 +/- 0.15). A 3.66-fold, 6.67-fold, 4.28-fold and 5.24-fold increases, in the (AbetaPP751 + AbetaPP770)/AbetaPP695 mRNA ratio were found in DLBc, DLBp, AD stage VC and AA, respectively, when compared with controls. No modifications in the ratio were found in PD, AD stage I-IIA and PSP. These findings suggest that alternative splicing of the APPP mRNA may play a role in betaA4 amyloidogenesis in DLBp, DLBc, AD stage VC and Amyloid angiopathy. (C) 2004 Elsevier Ltd. All rights reserved.
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