Neuroautoimmunity: Pathogenic Implications for Alzheimer’s Disease

Singh, Vijendra K.

doi:10.1159/000213837

Cited by 53 publications

(21 citation statements)

References 66 publications

(109 reference statements)

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“…AD is characterized by gradually progressing neuropsychiatric manifestations, and there are data indicating th.at excitotoxicity and oxidative damage could be involved (11). Stimulated immunocompetent cells are an important source of reactive oxygen species, and several studies have shown altered cell -mediated unmunity in the peripheral blood of patients with AD (2,(20)(21)(22)(23). These previous fmdings of a peripheral immune dysregulation in AD are underscored by our data.…”

Section: Discussionsupporting

confidence: 63%

“…At least it is an astonishing fmding that the concentrations of immune parameters in serum correlate with the cognitive capability of patients with AD. Numerous cytokines such as interleukin-l, interleukin-2, interleukin-6 and TNF-a have been shown to directly affect brain activity (9,23,35). Brain injury, a risk factor for AD, is associated with increased IL-l and increased APP-synthesis (42).…”

Section: Discussionmentioning

confidence: 99%

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Peripheral Immune Activation in Alzheimer's Disease

Leblhuber¹,

Walli²,

Tilz

et al. 2000

Pteridines

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In fifty-four patients with Alzheimer's disease [AD (14 males, 40 females, age 77 .1 2: 7.4 years)], free of any infection and twenty-two age-matched healthy controls with normal mental status (9 males, 13 females, age 74.9 ± 9.0 years) serum concentrations of soluble parameters of immune activation including neopterin, 55 kDa-type soluble tumor necrosis factor receptor (sTNF-RSS), soluble interleukin-2 receptor (sIL-2R), immunoglobulins A, M and G, complement components C3 and C4, circulating immune complexes, and soluble CD23 as well as a panel of routine laboratory tests were determined.Compared to controls, significantly higher concentrations of sIL-2R (p < 0.01), neopterin (p < 0.01), sTNF-R55. sCD23 and IgA (all p < O.OS) were found in AD patients. Patients with greater cognitive impairment had higher concentrations of neopterin and sTNF-R55 . An inverse correlation was seen between mini mental state (MMS) and sTNF-R55 (r = -0.43S; P < 0.01) and neopterin (rs = -0.289; P < 0.05). Our data show increased serum concentrations of immune activation markers in patients with AD correlating with the severity of dementia. Increased neopterin concentrations together with increased slNF-R55 and sIL-2R imply a chronic state of peripheral immune activation in the course of AD. Our data underscore previous reports on the effect of anti-inflammatory drugs in therapy and prevention of AD.

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Section: Discussionsupporting

confidence: 63%

Section: Discussionmentioning

confidence: 99%

Peripheral Immune Activation in Alzheimer's Disease

Leblhuber¹,

Walli²,

Tilz

et al. 2000

Pteridines

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“…Inflammatory cytokines, activated microglia, and immigration of certain T lymphocytes are found in association with AD neuropathologies, including amyloid plaques and neurofibrillary tangles (McGeer et al, 1989;Griffin et al, 1995;Singh, 1997;Neuroinflammation Working Group, 2000), and alterations in peripheral immune cells are also reported in patients with AD. The proportion of both CD4+ (Lombardi et al,.…”

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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“…Despite the vast amount of literature on nonspecific immune mechanisms in AD, little is known about the role of antigen-specific immune responses. Previous reports suggested that autoimmune mechanisms could contribute to the pathogenesis of AD Giubilei et al [5,6], while recent results on PDAPP transgenic mice immunized with Aß have highlighted the possible protective role of the antigen-specific immune responses [7].…”

Section: Introductionmentioning

confidence: 99%

T Cell Response to Amyloid-β and to Mitochondrial Antigens in Alzheimer’s Disease

Giubilei¹,

Antonini²,

Montesperelli³

et al. 2003

Dement Geriatr Cogn Disord

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Despite the vast amount of literature on non-specific immune mechanisms in Alzheimer’s disease (AD), little is known about the role of antigen-specific immune responses. We investigated T cell reactivity to fragment 1–42 of amyloid-β (Aβ) and to N-terminal peptides of human mitochondrial and control microbial proteins. Thirty subjects with a diagnosis of probable AD according to NINCDS-ADRDA criteria and 30 sex- and age-matched healthy controls were enrolled. T cell responses to Aβ fragment showed no significant differences between AD patients and controls. By contrast, the mean number of positive T cell responses to both human mitochondrial and microbial peptides was significantly decreased in AD patients compared to control subjects. No significant correlation was found between T cell responses and both the severity of cognitive impairment and duration of the disease. Our results suggest that antigen-specific immune responses are impaired in AD. Protective immune responses to harmful amyloidogenic substances may also be impaired, thus favoring their accumulation in the brain.

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Neuroautoimmunity: Pathogenic Implications for Alzheimer’s Disease

Cited by 53 publications

References 66 publications

Peripheral Immune Activation in Alzheimer's Disease

Peripheral Immune Activation in Alzheimer's Disease

Immunophenotypes in the circulation of patients with mild cognitive impairment

T Cell Response to Amyloid-β and to Mitochondrial Antigens in Alzheimer’s Disease

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