Enhanced production of amyloid precursor protein mRNA by peripheral mononuclear blood cell in Alzheimer's disease

Abstract

Previous studies have suggested the involvement of amyloid precursor protein (APP) in Alzheimer's disease (AD), as exons 16 and 17 of the APP gene mutations have been found in some familial AD patients. Furthermore, overexpression and deposition of the beta amyloid peptide, a proteolytic product of APP, have been considered as a pathological hallmark of Alzheimer's disease. Therefore, it is of particular interest to determine the expression of APP gene at the transcription level for better understanding of the roles of APP gene in AD pathogenesis. In this work, we employed the quantitative reverse transcriptase-polymerase chain reaction (RT-PCR) to quantify APP mRNA transcripts in the peripheral mononuclear blood cells (PMBC) of 52 Alzheimer's patients, 28 vascular dementia (VD) patients, and 60 healthy elderly controls. The results showed that the amount (mean +/- SEM) of APP transcripts per microgram of total cDNA was 4.05 +/- 0.27, 2.73 +/- 0.33, and 2.59 +/- 0.27 amole in AD, VD, and healthy controls, respectively. There was a significant increase (P < 0.05) in the expression of APP mRNA transcripts in AD compared with that in VD or in healthy controls. Thus, our data indicated that variation of APP gene expression in PMBC might be a pathogenic source of Alzheimer's disease.

Immunophenotypes in the circulation of patients with mild cognitive impairment

“…Increased expression of APP mRNA and protein in lymphocytes and monocytes has been demonstrated in AD patients, suggesting that the same alterations in APP expression leading to amyloid deposition in the brain may be reflected in peripheral immune cells (Pallister et al, 1997;Jung et al, 1999;Jiang et a., 2003) and/or potentially be a source for abnormal amyloid deposited in the brain (Allen et al, 1991;Reale et al, 2005). We investigated APP and Aβ expression in lymphocytes and monocytes from subjects with MCI to determine if similar alterations could be observed in a preclinical stage of AD.…”

“…Leukocytes also express APP mRNA and protein (Allen et al, 1991;Schlossmacher et al, 1992;Bullido et al, 1996), and APP expression on lymphocytes and monocytes can be increased with activating signals (Li et al, 1999;Bullido et al, 1996). Moreover, APP mRNA in PBMCs and APP protein in lymphocytes and monocytes have been found to be elevated in AD patients compared to controls (Jiang et al, 2003). Functional changes in APP production and processing in peripheral immune cells may reflect dysregulation of APP metabolism in the brain (Pallister et al, 1997;Jung et al, 1999).…”

Increased production of inflammatory cytokines in mild cognitive impairment

“…Interleukin-1 (IL-1) is associated with amyloid-β (Aβ) in senile plaques, hallmarks of AD neuropathology, (Griffin et al, 1989(Griffin et al, , 1995 and also increases the synthesis and translation of the mRNA for amyloid precursor protein (APP), the processing of which produces Aβ (Goldgaber et al, 1989;Rogers et al, 1999). Blood cells express APP mRNA and protein (Allen et al, 1991;Schlossmacher et al, 1992), and APP mRNA is increased in peripheral blood mononuclear cells (PBMCs) from AD patients compared with cells from healthy elderly controls (Jiang et al, 2003). This could potentially be a source for abnormal amyloid deposited in the brain (Allen et al, 1991;Reale et al, 2005).…”

Soluble amyloid precursor protein β as blood-based biomarker of Alzheimer’s disease

“…sAPPβ levels were decreased in our study compared with healthy aging and a non-Aβ type of dementia, which is in line with a reduced concentration of sAPPβ in AD brain cortex. 8 Even though increased concentrations of full-length APP protein in blood platelets and APP mRNA levels in blood mononuclear cells have been reported in AD, 9, 10 peripheral changes of APP cleavage products may be more closely related to cerebral changes due to AD than to a pathological response in the periphery. That is reduced sAPP levels possibly mirror decreased cortical APP expression in AD, which limits APP clearance across the blood-brain-barrier and/or decreased processing of APP into sAPP in blood.…”