Concurrent tau pathologies in frontotemporal lobar degeneration with TDP-43 pathology

Aims: Accumulating evidence suggests that patients with frontotemporal lobar degeneration (FTLD) can have pathologic accumulation of multiple proteins, including tau and TDP-43. This study aimed to determine the frequency and characteristics of concurrent tau pathology in FTLD with TDP-43 pathology (FTLD-TDP). Methods: The study included 146 autopsy-confirmed cases of FTLD-TDP and 55 cases of FTLD-TDP with motor neuron disease (FTLD-MND). Sections from the basal forebrain were screened for tau pathology with phospho-tau immunohistochemistry. For cases with tau pathology on the screening section, additional brain sections were studied to establish a diagnosis. Genetic analysis of C9ORF72, GRN, and MAPT was performed on select cases. Results: Among 201 cases, we found 72 cases (36%) with primary age-related tauopathy (PART), 85 (42%) with aging-related tau astrogliopathy (ARTAG), 45 (22%) with argyrophilic grain disease (AGD), and 2 cases (1%) with corticobasal degeneration (CBD). Patients with ARTAG or AGD were significantly older than those without these comorbidities. One of the patients with FTLD-TDP and CBD had C9ORF72 mutation and relatively mild tau pathology, consistent with incidental CBD. Conclusion: The coexistence of TDP-43 and tau pathologies was relatively common, particularly PART and ARTAG. Although rare, individual patients with FTLD can have multiple concurrent proteinopathies. The absence of TDP-43-positive astrocytic plaques may suggest that CBD and FTLD-TDP were independent disease processes in the two patients with both tau and TDP-43 pathologies. It remains to be determined if mixed cases represent a unique disease process or two concurrent disease processes in an individual.

Amyotrophic Lateral Sclerosis and Multiple Sclerosis: More Evidence Suggesting a Link

Objectives Previous reports of the concurrence of multiple sclerosis (MS) and amyotrophic lateral sclerosis (ALS) in the same patients suggest shared pathogenesis, with the C9orf72 mutation as a possible shared genetic link. Methods: Symptoms, neuroimaging, and laboratory data were summarized for patients with ALS and MS within our ALS registry. Using age adjusted MS prevalence rates, we calculated the expected co-occurrence using the binomial test. Results: Clinical and demographic features of the five patients (four female, one male) with ALS and MS are described. Because ALS more frequently occurs in men, observing 4/5 female patients with concurrent ALS/MS showed a borderline expectation difference (P=0.073). The observed co-occurrence of ALS and MS was 5X times higher than the expected frequency of 0.98 (P <0.004). Four patients were found negative for C9orf72. Discussion: Our results suggest a non-random association between MS and ALS, although shared genetic etiology was not found.