Add Alzheimer’s disease to the list of autoimmune diseases
Section snippets
Autoimmunity
The immune system protects the body from potentially harmful substances (antigens), such as foreign microorganisms, toxins, etc. The antigens are presented to cells that make specific antibodies, which ultimately lead to the destruction of the antigens. Unfortunately, these antigens may include “self” antigens leading to inappropriate destruction of normal body tissues (autoimmunity). Hence, normally occurring “harmless” host proteins can now become the target of the immune system. Autoimmunity
Blood–brain barrier dysfunction
As mentioned, autoimmune diseases can include the CNS. However, in order for any of the immunoglobulins to penetrate the brain, there must be an impaired ability to maintain the integrity of the blood–brain-barrier (BBB), a major modulator or filter of nutrient delivery to the CNS that is primarily constructed of endothelial cells and astrocytes [17], [18], [19]. Disturbances in the BBB can occur in head trauma [20], and conditions commonly associated with aging, such as atherosclerosis [21],
The AD autoimmune hypothesis
Immunoglobulins (Ig) have been detected in AD serum, CSF and in amyloid plaques and are associated with vessel-associated amyloid, which has been attributed due to a faulty BBB [38], [40], [46], [47], [48]. Furthermore, several additional reports have demonstrated the presence of Igs in neurons [46], [48], [49], [50] but none of those studies provided specifics as to percentage of neurons positive for Ig in the tissues, subcellular localization of the Ig labeling, and so forth. Unfortunately,
Acknowledgement
We express our deepest gratitude for the many constructive conversations on Alzheimer’s disease research with Drs. Robert Nagele, Daniel Lee, Hoau-Yan Wang and Stanley Belkowski, and for the technical expertise of Brenda Hertzog, Danielle Lawrence, Meghan Towers and Debbie Polkovitch.
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Harmony of T cell profile in brain, nasal, spleen, and cervical lymph nodes tissues in Alzheimer's: A systemic disease with local manifestations
2021, International ImmunopharmacologyCitation Excerpt :In addition, based on the T-helper profile observed in DCLN and SCLN of AD model, epitope spreading may occur in AD model similar to the phenomenon observed in EAE [29,52,53]. Consistently, such similarities provide more evidences on autoimmune nature of AD [15–17]. Lessons learnt from the similarity between tumor immunology and AD such as aberrant angiogenesis, increase of regulatory T cells, chronic inflammation, and hypoxia [54] suggest AD as a systemic disease with local manifestations similar to tumor [55,56].
Possible dementia risk of proton pump inhibitors and H2 receptor blockers use in the treatment of Helicobacter pylori: A meta-analysis study
2020, Medical HypothesesCitation Excerpt :Recently, a link between Helicobacter pylori and extra-digestive disorders was found. Some of those disorders, which include atherosclerosis [11], hypertension, and stroke [12], were also related to increased risk of Alzheimer’s disease through damage to the blood–brain barrier [13–15]. However, Helicobacter pylori were not directly related to the occurrence of all-cause dementia [16].
Towards an understanding of women's brain aging: the immunology of pregnancy and menopause
2020, Frontiers in NeuroendocrinologyCitation Excerpt :The prevalence of Alzheimer’s disease (AD) is higher in women compared to men in most regions of the world (Winblad et al., 2016; Nichols et al., 2019), particularly in older age (Miech et al., 2002; Roberts et al., 2014, Fratiglioni et al., 1997). AD pathogenesis involves inflammatory processes (Wyss-Coray and Rogers, 2012) and autoimmune activity (Fymat, 2018; D’Andrea, 2005; Sardi et al., 2011), and several types of autoimmune diseases have been linked to increased risk for AD (Wotton and Goldacre, 2017). Women are in general more frequently affected by autoimmune diseases than men (Whitacre, 2001; Ngo et al., 2014), and the female to male ratio has been shown to be 3:1 for multiple sclerosis (MS), 7:1 for rheumatoid arthritis (RA), and up to 16:1 for Sjögren’s syndrome (Natri et al., 2019).
Controversial Past, Splendid Present, Unpredictable Future: A Brief Review of Alzheimer Disease History
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