Detection of distinct isoform patterns of the β-amyloid precursor protein in human platelets and lymphocytes

Schlossmacher, Michael G.; Ostaszewski, Beth L.; Hecker, Lanny I.; Celi, Alessandro; Haass, Christian; Chin, David A.; Lieberburg, Ivan; Furie, Barbara C.; Furie, Bruce; Selkoe, Dennis J.

doi:10.1016/0197-4580(92)90117-g

Cited by 59 publications

(15 citation statements)

References 72 publications

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“…Trieb et al (1996)have shown that lymphocyte proliferation is stimulated by amyloid precursor protein (APP), the processing of which produces amyloid-β (Aβ) peptide, the major component of amyloid plaques (Mott et al, 2005), in control but not AD patients. 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).…”

Section: Introductionmentioning

confidence: 99%

Immunophenotypes in the circulation of patients with mild cognitive impairment

Magaki

Yellon

Mueller

et al. 2008

Journal of Psychiatric Research

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Alterations in the peripheral immune system are associated with dementia and the neuropathology of Alzheimer's disease, but have yet to be studied early in the disease process. To test the hypothesis that the balance of immune cell phenotypes is disrupted in the early progression of memory deterioration, patients with mild cognitive impairment (MCI) and healthy elderly controls were examined for the distribution of subpopulations of leukocytes (lymphocytes, granulocytes, and monocytes) and lymphocyte subtypes (helper/inducer and suppressor/cytotoxic T lymphocytes and B lymphocytes) in blood. MCI subjects had a significantly higher percentage of total lymphocytes and a lower percentage of granulocytes compared to elderly controls. Furthermore, the expression of cell surface amyloid precursor protein (APP) and intracellular amyloid-β peptide (Aβ) in lymphocytes and monocytes were determined. We found lymphocyte APP expression to be significantly increased in MCI subjects compared to controls. Our data indicate that changes in immunological parameters may be detected early in MCI, and an alteration of the immune response may precede clinical AD.

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Section: Introductionmentioning

confidence: 99%

Immunophenotypes in the circulation of patients with mild cognitive impairment

Magaki

Yellon

Mueller

et al. 2008

Journal of Psychiatric Research

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“…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).…”

Section: Introductionmentioning

confidence: 99%

Increased production of inflammatory cytokines in mild cognitive impairment

Magaki

Mueller

Dickson

et al. 2007

Experimental Gerontology

139

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Recent studies indicate that chronic inflammation plays a pathogenic role in both the central nervous system (CNS) and periphery in Alzheimer's disease (AD). We have screened for cytokines differentially produced by peripheral blood mononuclear cells (PBMCs) isolated from subjects with mild cognitive impairment (MCI) and mild AD subjects who had progressed from MCI using a commercially available cytokine array. Following determination of expressed cytokines, we quantified levels of the proinflammatory cytokines TNF-α, IL-6, and IL-8, and the antiinflammatory cytokine IL-10 using flow cytometry. We have found a significant increase in the levels of IL-6, IL-8, and IL-10 produced by PBMCs stimulated for 24 hours with phytohemagglutinin (PHA) in MCI subjects compared to healthy elderly controls. However, in PBMCs stimulated for 48 h with lipopolysaccharide (LPS), lower TNF-α/IL-10, IL-6/IL-10, and IL-8/IL-10 ratios were seen in MCI subjects. There were no differences in plasma levels of IL-8 between aged controls, MCI, and mild AD, and the levels of circulating IL-6 and IL-10 were below detection limits. Our data indicate that changes in cytokine production by PBMCs may be detected early in MCI, and an alteration of the immune response may precede clinical AD.

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“…Moreover, Shinitzky et al (1991) detected serum antiplatelet antibodies for dementia patients. This is interesting, given the presence of full-length amyloid precursor protein in platelets that might serve as a circulating source for amyloid beta protein (ABP) (Schlossmacher et al, 1992). A recent study showed that non-CNS autoantibodies were equally common for patients with probable AD and controls (Lopez et al, 1991).…”

Section: Discussionmentioning

confidence: 97%

Circulating immune complexes in sera from patients with Alzheimer's disease and subjects with age-associated memory impairment

Op¹,

Hallikainen²,

Hänninen³

et al. 1993

J Neural Transm Gen Sect

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Before, we reported a higher frequency of circulating immune complexes (CIC) in the sera from institutionalized Alzheimer's disease (AD), multi-infarct dementia and Down's syndrome patients than from age-matched controls. In this study, we tested the presence of CIC in the sera from an extended series of hospitalized AD patients, AD patients living in the community, from age-associated memory impairment (AAMI) subjects as well as from nursing home and community controls. We used two methods to measure CIC, C1q binding Elisa (C1qB-Elisa) and conglutinin binding (KgB-Elisa). The AD patients showed the highest frequency of positive findings and differed from the controls in KgB (42% vs. 17%) (Chi-square, p = 0.01) and C1qB (30% vs. 11%) (p < 0.05). In severe AD, 14/19 patients were KgB positive and 11/19 were C1qB positive and differed from controls. The frequency of CIC for the patients with moderate or mild dementia, the AAMI subjects and controls was similar. In the multivariate linear regression analysis, high CIC values of the AD patients significantly associated with a long disease duration and a history of recurrent urinary infections but not with age, sex, hospitalization, or the Mini-Mental Status score. We conclude that AD patients with severe dementia frequently show CIC but those with mild or moderate disease do not. The CIC relate to a long disease duration and a history of recurrent urinary infections.

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Detection of distinct isoform patterns of the β-amyloid precursor protein in human platelets and lymphocytes

Cited by 59 publications

References 72 publications

Immunophenotypes in the circulation of patients with mild cognitive impairment

Immunophenotypes in the circulation of patients with mild cognitive impairment

Increased production of inflammatory cytokines in mild cognitive impairment

Circulating immune complexes in sera from patients with Alzheimer's disease and subjects with age-associated memory impairment

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