Beta-Amyloid Peptides Enhance the Proliferative Response of Activated CD4+CD28+ Lymphocytes from Alzheimer Disease Patients and from Healthy Elderly

Abstract

Alzheimer's disease (AD) is the most frequent form of dementia among elderly. Despite the vast amount of literature on non-specific immune mechanisms in AD there is still little information about the potential antigen-specific immune response in this pathology. It is known that early stages of AD include β-amyloid (Aβ)- reactive antibodies production and inflammatory response. Despite some evidence gathered proving cellular immune response background in AD pathology, the specific reactions of CD4+ and CD8+ cells remain unknown as the previous investigations yielded conflicting results. Here we investigated the CD4+CD28+ population of human peripheral blood T cells and showed that soluble β-amyloids alone were unable to stimulate these cells to proliferate significantly, resulting only in minor, probably antigen-specific, proliferative response. On the other hand, the exposure of in vitro pre-stimulated lymphocytes to soluble Aβ peptides significantly enhanced the proliferative response of these cells which had also lead to increased levels of TNF, IL-10 and IL-6. We also proved that Aβ peptide-enhanced proliferative response of CD4+CD28+ cells is autonomous and independent from disease status while being associated with the initial, ex vivo activation status of the CD4+ cells. In conclusion, we suggest that the effect of Aβ peptides on the immune system of AD patients does not depend on the specific reactivity to Aβ epitope(s), but is rather a consequence of an unspecific modulation of the cell cycle dynamics and cytokine production by T cells, occurring simultaneously in a huge proportion of Aβ peptide-exposed T lymphocytes and affecting the immune system performance.

Chronic Psychosis and its Prevention

“…In Alzheimer's disease the peripheral lymphocytes respond poorly to mitogenic stimulation. The same phenomenon was found in chronic schizophrenia [14][15][16]. This may open a diagnostic window for early detection and prevention of these conditions (first pillar of interventions).…”

Adaptive lymphocyte profiles correlate to brain Aβ burden in patients with mild cognitive impairment

“…Others have also observed no correlation of activated CD4 T cells with a battery of cognitive domain tests in aMCI subjects ( n = 19) [ 29 ]. It is thought that T cells in the CSF would typically mediate an Aβ 42 -directed immune response to clear amyloid from the brain [ 37 ], which should result in improved cognition and brain health. However, the aMCI cohorts in our study or the Lueg study do not support this concept.…”

Reduced β-amyloid pathology in an APP transgenic mouse model of Alzheimer’s disease lacking functional B and T cells

“…Richart-Salzburger, for example, reported a significant decrease of CD3 + CD8 + and CD19 + lymphocytes in the peripheral blood of Alzheimer’s disease patients, suggesting a general decline of the adaptive immunity in disease pathogenesis [ 31 ]. Other authors, in contrast, observed significant increases in activated CD4 + and CD8 + T cell subsets in peripheral blood [ 32 – 35 ]. Recently, Lueg et al also assessed alterations of T cell subsets in the intrathecal compartment of cognitively impaired and cognitively intact elderly subjects as well as healthy younger control individuals and found a significantly increased proportion of CD8 + lymphocytes in the CSF of patients with Alzheimer’s disease – but not in patients suffering from other dementias – which correlated with cognitive deficits [ 33 ].…”