Amyloid precursor protein mRNA levels in Alzheimer's disease brain

• Insoluble beta-amyloid deposits in Alzheimer's disease (AD) brain are proteolytically derived from the membrane bound amyloid precursor protein (APP). The APP gene is differentially spliced to produce isoforms that can be classified into those containing a Kunitz-type serine protease inhibitor domain (K(+), APP(751), APP(770), APRP(365) and APRP(563)), and those without (K(-), APP(695) and APP(714)). Given the hypothesis that Abeta is a result of aberrant catabolism of APP, differential expression of mRNA isoforms containing protease inhibitors might play an active role in the pathology of AD. We took 513 cerebral cortex samples from 90 AD and 81 control brains and quantified the mRNA isoforms of APP with TaqMan real-time RT-PCR. After adjustment for age at death, brain pH and gender we found a change in the ratio of KPI(+) to KPI(-) mRNA isoforms of APP. Three separate probes, designed to recognise only KPI(+) mRNA species, gave increases of between 28% and 50% in AD brains relative to controls (p=0.002). There was no change in the mRNA levels of KPI-(APP 695) (p=0.898). Therefore, whilst KPI-mRNA levels remained stable the KPI(+) species increased specifically in the AD brains.

Ämnesord

MEDICIN OCH HÄLSOVETENSKAP  -- Medicinska och farmaceutiska grundvetenskaper -- Neurovetenskaper (hsv//swe)

MEDICAL AND HEALTH SCIENCES  -- Basic Medicine -- Neurosciences (hsv//eng)

NATURVETENSKAP  -- Biologi -- Genetik (hsv//swe)

NATURAL SCIENCES  -- Biological Sciences -- Genetics (hsv//eng)

Nyckelord

Adult

Aged

Aged; 80 and over

Alzheimer Disease/*metabolism

Amyloid beta-Protein Precursor/classification/genetics/*metabolism

Analysis of Variance

Case-Control Studies

Cerebral Cortex/*metabolism

Comparative Study

Female

Glial Fibrillary Acidic Protein/analysis/genetics

Humans

Linear Models

Male

Microtubule-Associated Proteins/analysis/genetics

Middle Aged

Protein Isoforms/analysis/classification/genetics

RNA; Messenger/metabolism

Reverse Transcriptase Polymerase Chain Reaction/methods

Sex Factors

Neurobiology

Neurobiologi

Genetics

Genetik

Publikations- och innehållstyp

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