title: Amyloid-beta deposition in the cerebral cortex in Dementia with Lewy bodies is accompanied by a relative increase in AbetaPP mRNA isoforms containing the Kunitz protease inhibitor.
abstract: Deposition of amyloid-beta, the fibrillogenic product of the cell surface protein AbetaPP (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 AbetaPP 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 (n=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 (A260/280 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 AbetaPP mRNA may play a role in betaA4 amyloidogenesis in DLBp, DLBc, AD stage VC and Amyloid angiopathy.
authors.affiliation: Institut de Neuropatologia, Servei Anatomia Patològica, IDIBELL-Hospital Universitari de Bellvitge, carrer Feixa Llarga sn, 08907 L'Hospitalet de Llobregat, Spain.
authors.forename: Marta
authors.initials: M
authors.lastname: Barrachina
authors.forename: Esther
authors.initials: E
authors.lastname: Dalfó
authors.forename: Berta
authors.initials: B
authors.lastname: Puig
authors.forename: Noemi
authors.initials: N
authors.lastname: Vidal
authors.forename: Meritxell
authors.initials: M
authors.lastname: Freixes
authors.forename: Esther
authors.initials: E
authors.lastname: Castaño
authors.forename: Isidro
authors.initials: I
authors.lastname: Ferrer
mesh_terms: D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D016229:Amyloid beta-Peptides / Q000235:genetics / Q000378:metabolism*; D016564:Amyloid beta-Protein Precursor / Q000096:biosynthesis* / Q000235:genetics; D007611:Aprotinin / Q000235:genetics*; D015153:Blotting, Western; D002540:Cerebral Cortex / Q000378:metabolism*; D018076:DNA, Complementary / Q000096:biosynthesis / Q000235:genetics; D005260:Female; D015870:Gene Expression / Q000502:physiology; D005904:Glial Fibrillary Acidic Protein / Q000096:biosynthesis / Q000235:genetics; D006801:Humans; D007536:Isomerism; D020961:Lewy Body Disease / Q000378:metabolism*; D008297:Male; D008875:Middle Aged; D009419:Nerve Tissue Proteins / Q000096:biosynthesis / Q000235:genetics; D012333:RNA, Messenger / Q000096:biosynthesis*; D020133:Reverse Transcriptase Polymerase Chain Reaction
chemical_list: D016229:Amyloid beta-Peptides; D016564:Amyloid beta-Protein Precursor; D018076:DNA, Complementary; D005904:Glial Fibrillary Acidic Protein; D009419:Nerve Tissue Proteins; D012333:RNA, Messenger; D007611:Aprotinin