Current Nosology of Neural Autoantibody-Associated Dementia

Hansen, Niels

doi:10.3389/fnagi.2021.711195

Cited by 12 publications

(13 citation statements)

References 69 publications

(127 reference statements)

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“…However, there have been no investigations addressing the progression of cognitive dysfunction in autoantibody-associated dementia compared to Alzheimer's dementia (AD). Recent individual case reports (5)(6)(7) and reviews (1,3) have postulated that rapidly progressing cognitive dysfunction associated with neural autoantibodies are a typical clinical manifestation of NABD. We thus conducted a pilot trial relying on retrospective data to identify whether progressing cognitive dysfunction is more prominent in NABD than in AD.…”

Section: Introductionmentioning

confidence: 99%

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Cerebrospinal Fluid Total Tau Protein Correlates With Longitudinal, Progressing Cognitive Dysfunction in Anti-Neural Autoantibody-Associated Dementia and Alzheimer’s Dementia: A Case–Control Study

et al. 2022

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BackgroundNeural autoantibody-associated dementia (NABD) is an increasing phenomenon in memory clinics with a high impact on later therapy. Biomarkers are lacking that differentiate this type of dementia from neurodegenerative dementia such as Alzheimer’s dementia (AD). Our aim is to analyze neurodegeneration markers and their relationship to progressing cognitive dysfunction in NABD and AD to test for tools differentiating these two forms of dementia prior to neural autoantibody testing.MethodsIn our retrospective, observational study, we investigated 14 patients with dementia and serum and/or cerebrospinal fluid (CSF) neural autoantibodies as well as 14 patients with AD by relying on recent CSF and clinical criteria for AD. Patient files were checked for psychopathology, neuropsychological test performance, autoimmune indicators, CSF, and MRI results.ResultsOur patient groups did not differ in their psychopathology, autoimmune indicators, or MRI profile. The progression of cognitive dysfunction [as measured by the difference in Mini-Mental State Examination (MMSE) scores since disease onset, and the yearly progression rate (MMSE loss/per year)] did not vary significantly between groups. Total tau protein was significantly higher in AD patients than NABD patients revealing no signs of Alzheimer’s disease pathology in their CSF (p < 0.05). Total tau protein levels in CSF correlated with cognitive decline since disease onset (r = 0.38, p < 0.05) and yearly progression rates (r = 0.56, p < 0.005) in all patients.DiscussionOur results suggest that the progression of cognitive dysfunction as defined by MMSE does not seem to be an appropriate biomarker for distinguishing NABD from AD. However, the total tau protein level in CSF might be a relevant molecular biomarker that can indicate disease pathology and/or progression in both known AD and NABD, which is often accompanied by axonal degeneration. Total tau protein may be an additional diagnostic tool with which to differentiate anti-neural-associated dementia from AD if further research confirms these proof-of-concept findings in larger patient cohorts.

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Section: Introductionmentioning

confidence: 99%

“…Neural autoantibody-associated dementia (NABD) ( 1 , 2 ) is a disease entity whose incidence is rising through the identification of novel neural autoantibodies in relationship to a clinical phenotype characterized by initial cognitive impairment. Recent progress has been made in classifying NABD ( 2 – 4 ).…”

Section: Introductionmentioning

confidence: 99%

Cerebrospinal Fluid Total Tau Protein Correlates With Longitudinal, Progressing Cognitive Dysfunction in Anti-Neural Autoantibody-Associated Dementia and Alzheimer’s Dementia: A Case–Control Study

et al. 2022

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“…Concurring with these signs of neurodegeneration in brain MRI, our CSF results deliver support, as we detected axonal degeneration in 75% via elevated tau and tau 181 protein. Axonal neurodegeneration may coincide with autoantibody-associated cognitive decline (16). Verbal memory involvement, with particular focus on memory recall in our patient with glycine-receptor antibodies is highly likely, as glycine receptors are expressed in the hippocampus (17).…”

Section: Discussionmentioning

confidence: 74%

Impaired Verbal Memory Recall in Patients With Axonal Degeneration and Serum Glycine-Receptor Autoantibodies—Case Series

et al. 2022

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BackgroundGlycine receptor antibody-associated neuropsychiatric disease is currently known to be dominated by the phenotypes stiff-person syndrome and progressive encephalomyelitis entailing rigidity and myoclonus. In our case series we aim to depict the less-often reported feature of cognitive impairment associated with glycine receptor antibodies.MethodsWe investigated five patients with cognitive impairment varying from mild cognitive impairment to dementia associated with serum glycine receptor antibodies. Mild and major neurocognitive disorders were diagnosed according to the DSM-5 (fifth edition of the Diagnostic and Statistical Manual of Mental Disorders). Neuropsychology via Consortium to Establish a Registry for Alzheimer's Disease (CERAD) testing results, psychopathology data via the Manual for the Assessment and Documentation of Psychopathology in Psychiatry (AMDP), cerebrospinal fluid analysis and magnetic resonance imaging data were retrospectively analyzed from patient files.ResultsWe identified five patients with cognitive impairment as the main neuropsychiatric feature associated with serum glycine receptor antibodies. One patient also presented akinetic rigidity syndrome. The psychopathology comprised disorders of attention and memory, orientation, formal thought, and affect. In addition to suffering deficits in verbal memory function, figural recall, phonematic fluency, and globally deteriorated cognitive function, these patients presented seriously impaired memory recall in particular. Tau protein and phosphorylated tau protein 181 were elevated in 75% of patients.ConclusionsOur results suggest that axonal neurodegeneration and especially impaired verbal memory recall in addition to deficits in verbal and figural memory characterize patients with progressive cognitive impairment associated with glycine receptor antibodies. This unresolved issue should be clarified by researchers to discover whether axonal degeneration is merely an age-related phenomenon or one related to glycine-receptor autoantibodies in old age. Cognitive impairment as a neuropsychiatric syndrome of glycine-receptor antibody disease is a potential, conceivable, but so far unproven additional feature requiring deeper large-scale investigations and consideration during differential diagnosis in memory clinics.

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“…This process may lead to the emergence of immune cells producing Ab reacting to surface proteins of intact neurons and other brain cells, as well as peptides and proteins released after their pathological breakdown 38 - 40 . Such autoimmune reaction has been implicated in autoimmune response-related psychosis and schizophrenia 41 , 42 as well as neural autoantibody-associated dementias (NABD) with signs of axonal degeneration 43 , 44 . Quantitative analysis and profiling of Aabs targeting neuronal proteins, may, therefore, provide specific and instructive information on the onset, mechanisms, and severity of brain pathology.…”

Section: Biology Of Aabs With Relevance To Nddsmentioning

confidence: 99%

Autoantibodies targeting neuronal proteins as biomarkers for neurodegenerative diseases

Kocurova¹,

Říčný²,

Ovsepian³

2022

Theranostics

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Neurodegenerative diseases (NDDs) are associated with the accumulation of a range of misfolded proteins across the central nervous system and related autoimmune responses, including the generation of antibodies and the activation of immune cells. Both innate and adaptive immunity become mobilized, leading to cellular and humoral effects. The role of humoral immunity in disease onset and progression remains to be elucidated with rising evidence suggestive of positive (protection, repair) and negative (injury, toxicity) outcomes. In this study, we review advances in research of neuron-targeting autoantibodies in the most prevalent NDDs. We discuss their biological origin, molecular diversity and changes in the course of diseases, consider their relevance to the initiation and progression of pathology as well as diagnostic and prognostic significance. It is suggested that the emerging autoimmune aspects of NDDs not only could facilitate the early detection but also might help to elucidate previously unknown facets of pathobiology with relevance to the development of precision medicine.

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Current Nosology of Neural Autoantibody-Associated Dementia

Cited by 12 publications

References 69 publications

Cerebrospinal Fluid Total Tau Protein Correlates With Longitudinal, Progressing Cognitive Dysfunction in Anti-Neural Autoantibody-Associated Dementia and Alzheimer’s Dementia: A Case–Control Study

Cerebrospinal Fluid Total Tau Protein Correlates With Longitudinal, Progressing Cognitive Dysfunction in Anti-Neural Autoantibody-Associated Dementia and Alzheimer’s Dementia: A Case–Control Study

Impaired Verbal Memory Recall in Patients With Axonal Degeneration and Serum Glycine-Receptor Autoantibodies—Case Series

Autoantibodies targeting neuronal proteins as biomarkers for neurodegenerative diseases

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