Role of Autoantibodies in Neurodegenerative Dementia: An Emerging Association

Abstract

<b><i>Objective:</i></b> In the background of an emerging role for immune dysregulation in neurodegenerative dementias, this study aimed to investigate the relationship between systemic autoimmunity and dementia. The objective was to study the frequency and profile of disease-specific autoantibodies in Alzheimer’s dementia (AD), frontotemporal dementia (FTD), and dementia with Lewy bodies (DLB). <b><i>Methods:</i></b> Immunological testing was performed in a large cohort of neurodegenerative dementia diagnosed based on standard clinical and imaging criteria. Patients were evaluated for the presence of autoantibodies specific for systemic autoimmune diseases that included anti-extractable nuclear antibody profile, rheumatoid factor antibody (RA), perinuclear anti-neutrophil cytoplasmic antibody (p-ANCA), and cytoplasmic anti-neutrophil cytoplasmic antibody (c-ANCA) in serum. <b><i>Results:</i></b> Of 174 patients with degenerative dementia (FTD = 114, AD = 53, and DLB = 7) evaluated with immunological testing, 18.9% (<i>n</i> = 33) were seropositive for autoantibodies. The common antibodies detected were anti-Scl-70 (25%), anti-Ro-52 (18.7%), anti-nRNP-Sm (12.5%), and anti-CENP-B (9.3%). There were no significant systemic complaints in the majority of patients. A wider range of antibodies were positive in FTD compared to AD and DLB. While no difference was observed in the mean age, sex, or duration of illness between seropositive and negative patients, family history of dementia was more frequent among seronegative patients. <b><i>Conclusion:</i></b> Our findings indicate an emerging role for immune dysregulation in patients with classical neurodegenerative dementias, especially those with FTD. These autoantibodies could play a role in immune degradation of protein aggregates that characterize neurodegeneration. Study findings emphasize the need to explore the complex relationship between systemic autoimmunity and neurodegenerative dementia.

Autoimmunity and Frontotemporal Lobar Degeneration: From Laboratory Study to Clinical Practice

“…75 Other Autoantibodies Related to FTLD Because a wide spectrum of autoantibodies has been found in FTLD patients, the connection of autoimmunity with FTLD seems to be more substantial than that for other neurodegenerative diseases causing dementia. 76 The presence of antinuclear antibody might be the initial disruptive event in the immune system. Then, changes in other autoantibodies with more directivity (eg, anti-dsDNA, anti-Sm) indicating a particular autoimmune disease could occur.…”

Profiling the autoantibody repertoire reveals autoantibodies associated with mild cognitive impairment and dementia

“…Autoantibodies have been detected in the blood and cerebrospinal fluid of patients with different forms of dementia, including autoimmune dementia and neurodegenerative dementias such as AD, vascular dementia (VD), FTD, and Lewy body dementia (DLB) (12)(13)(14)(15)(16). Autoimmune dementia is a progressive cognitive impairment characterised by early onset, atypical clinical presentation and rapid progression associated with neural antibodies, inflammation in cerebrospinal fluid, brain changes in MRI atypical for neurodegenerative disease, and a good response to immunotherapy (17).…”

Biomarkers of neurodegeneration in neural autoantibody-associated psychiatric syndromes: A retrospective cohort study

“…Neurodegenerative biomarkers can also be elevated in psychiatric patients presenting autoantibody evidence who fail to fulfill AE criteria [ 16 ]. Although a dysregulated immune system is thought to play a major role in neurodegenerative processes [ 17 ], the exact role played by both autoantibodies and elevated neurodegeneration markers remains unclear in many of these diseases [ 18 , 19 ]. Clear answers to these questions would influence further diagnostic and therapeutic options for psychiatric disorders, and thus have direct consequences for the individual patient.…”