Metabolic Abnormalities in Alzheimer Disease

DOI: 10.1007/978-0-387-79112-8_22 In book: Metabolic Encephalopathy, pp.483-530


In 1906, German neuropathologist and psychiatrist Alois Alzheimer described “eine eigenartige Erkrankung der Hirnrinde” (a
peculiar disease of the cerebral cortex). Alzheimer noted two abnormalities in autopsied brain tissue from his index case:
senile plaques, proteinaceous structures previously described in the brain of normal elderly people; and abnormal cells delineated
with silver stain that became known as neurofibrillary tangles (NFTs). The distribution and abundance of tangle-filled neurons
are now the main criteria used to diagnose Alzheimer disease (AD) at autopsy.

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    ABSTRACT: Quantitative real-time reverse transcription-polymerase chain reaction (qRT-PCR) is a popular technique for mRNA expression studies. Normalization to an endogenous reference transcript (housekeeper) is widely used to correct for differences in loading and RNA quality. Alzheimer's disease (AD) alters brain metabolism. The stability of housekeeper transcript expression must be carefully validated. qRT-PCR was used to assess eight putative housekeeper transcripts in four brain regions from 15 control, 12 AD, and 10 AD/Lewy body disease (LBD) cases. RNA quality is lower in AD and AD/LBD than in controls. Frequently used housekeepers such as glyceraldehyde-3-phosphate dehydrogenase (GAPDH) and β-actin had lower overall expression in AD and AD/LBD cases than in controls. RPL13 and 18S were the most stably expressed housekeepers tested. Synaptophysin and glial fibrillary acidic protein were used to evaluate normalized quantification. By using different housekeepers we confirmed that synaptophysin expression was down-regulated in AD cases, whereas glial fibrillary acidic protein expression was increased. Among all candidates tested, RPL13 was the best housekeeper for qRT-PCR studies in autopsy brain tissue samples from controls and AD cases. RNA quality should be assessed and data normalized on this index as well.
    Alzheimer's & dementia: the journal of the Alzheimer's Association 11/2010; 6(6):465-74. DOI:10.1016/j.jalz.2009.11.002 · 12.41 Impact Factor