Microglial and Neuronal TDP-43 Pathology in Anti-IgLON5-Related Tauopathy

Cagnin, Annachiara; Mariotto, Sara; Fiorini, Michele; Gaule, Marina; Bonetto, Nicola; Tagliapietra, Matteo; Buratti, Emanuele; Zanusso, Gianluigi; Ferrari, Sergio; Monaco, Salvatore

doi:10.3233/jad-170189

Cited by 42 publications

(29 citation statements)

References 14 publications

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“…Absence of brainstem pTau pathology was also previously reported in the autopsy of a 69-year-old woman with IgLON5 antibodies. 5 She had mild neuronal pTau pathology preferentially in temporomedial regions suggestive of primary agerelated tauopathy (PART). 8 Similar to our case, CD4 and CD8 perivascular T-lymphocytes and few CD20 B-lymphocytes were found in the thalamus, basal ganglia, and mesencephalon.…”

Section: Discussionmentioning

confidence: 99%

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Anti-IGLON5 disease

Erro

Sabater

Martı́nez

et al. 2020

Neurol Neuroimmunol Neuroinflamm

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ObjectiveTo describe the neuropathologic features and the molecular data of phosphorylated tau (pTau) in a new case of anti-IgLON5 disease.MethodsReview of clinical data, postmortem neuropathologic examination. Biochemical analyses of pTau were performed in brain samples from the present case and from a previously described patient with anti-IgLON5 with the characteristic brainstem tauopathy.ResultsThe patient was a 71-year-old man with a clinical syndrome consisting of sleep disturbance and bulbar symptoms. IgLON5 antibodies of predominant IgG4 subtype were detected in serum and CSF. He carried the HLA DRB1*10:01-DQB1*05:01 haplotype. Despite treatment with IV immunoglobulins, he unexpectedly died during sleep 2 years after disease onset. Histology showed neurofibrillary pathology and β-amyloid deposits consistent with Alzheimer disease (AD) of intermediate severity. pTau deposits were absent in the brainstem. There were few perivascular CD8+ T-cell infiltrates in the posterior hypothalamus, amygdala, and brainstem with microglial activation. The pTau immunoblot showed a pattern of bands consistent with AD, which was different from that observed in the patient with anti-IgLON5 with brainstem tauopathy who presented a differential band around 56 KDa.ConclusionThe absence of pTau deposits in the brainstem of the present patient suggests that the tauopathy of patients with anti-IgLON5 disease may be a late, secondary event. The anti-IgLON5 brainstem tauopathy has a specific molecular signature different from primary tauopathies. pTau deposits restricted to the hippocampus/limbic regions of patients with anti-IgLON5 may represent an age-related comorbidity.

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Section: Discussionmentioning

confidence: 99%

“…2 Since the initial descriptions, the brain biopsy in 2 cases and the autopsy in another have not shown these particular tauopathy. [3][4][5] We present the neuropathologic features and the molecular data of phosphorylated tau (pTau) in a new anti-IgLON5 patient.…”

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confidence: 99%

Anti-IGLON5 disease

Erro

Sabater

Martı́nez

et al. 2020

Neurol Neuroimmunol Neuroinflamm

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“…The literature search initially retrieved 113 studies published between 2014 and 2019, from which 35 were excluded as duplicates, 38 after reading the title and abstract and 22 after reading the whole article (Table S1). Therefore, 18 articles met the selection criteria (see Figure 1): three case series 1,7,8 and 15 case reports, [11][12][13][14][15][16][17][18][19][20][21][22][23][24][25][26][27][28] all with a SIGN level of evidence of 3, which described a total of 46 patients with IgLON5 treated with IT (Table 1).…”

Section: Searchmentioning

confidence: 99%

Response to immunotherapy in anti‐IgLON5 disease: A systematic review

et al. 2020

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The aim of this study was to evaluate the frequency of response to immunotherapy in patients with anti‐IgLON5 disease through a systematic review of the literature. MEDLINE and Embase databases were searched for studies that included patients with anti‐IgLON5 disease who received immunotherapy (IT). Review inclusion criteria were met by 18 studies. The main study variable was response to IT, defined as the frequency of patients with an improvement greater than mild in at least one of the main symptoms defined by the clinical phenotype. Data were also gathered on the rate of response to last follow‐up, the line(s) of IT received, the administration of monotherapy or combination therapy, and clinical and analytical characteristics. Selected studies included a total of 46 patients. A response to IT was observed in 20 (43.4%) and the presence of response to last follow‐up in 15 (32.6%). Response was achieved more frequently with combination therapy vs monotherapy (14/21 [66.6%] vs 7/22 [31.8%]) and second‐line therapy vs first‐line therapy (7/13 [53.8%] vs 15/46 [32.6%]). The response rate by drug was 34.2% (12/35) for steroids, 42.8% (9/21) for IVIg, 46% (7/15) for PLEX, 100% (5/5) for AZA and 75% (3/4) for MMF. Factors associated with a response to IT included the cognitive impairment and non‐classical phenotypes, presence of HLA‐DQB1*05:01 without HLA‐DRB1*10:01 and cerebral spinal fluid inflammation. Patients with anti‐IgLON5 disease respond to IT, and this response is associated with certain clinical and analytical characteristics of the patients. Also rate of response seems higher with second‐line and combination treatment. However, the quality of available studies is inadequate to allow definitive conclusions to be drawn.

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“…Moreover, most patients were unresponsive to immunotherapy [3]. Recent studies, however, may have investigated a higher number of patients in more advanced disease stages where immunosuppressive therapy may have been insufficient due to advanced neuroinflammation and subsequent taurelated neurodegeneration [1,4]. Although the syndrome is typically characterized by a combination of several neurological signs, monosymptomatic or oligosymptomatic disease courses may exist at least in early stages [5].…”

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confidence: 99%