Argyrophilic Grain Pathology in Frontotemporal Lobar Degeneration: Demographic, Clinical, Neuropathological, and Genetic Features

Article type: Research Article

Authors: Gil, María José^{a; b; *} | Manzano, María Sagrario^c | Cuadrado, María Luz^d | Fernández, Cristina^e | Góméz, Elena^b | Matesanz, Carmen^f | Calero, Miguel^{b; f} | Rábano, Alberto^b

Affiliations: [a] Servicio de Neurología, Hospital Universitario de Torrejón, Torrejón de Ardoz, Madrid, Spain | [b] Banco de Tejidos, Departamento de Neuropatología, Fundación Centro de Investigación en Enfermedades Neurológicas, Instituto de Salud Carlos III (FCIEN-ISCIII), Madrid, Spain | [c] Servicio de Neurología, Hospital Universitario Infanta Cristina, Parla, Madrid, Spain | [d] Servicio de Neurología, Hospital Clínico San Carlos, Departamento de Medicina, Universidad Complutense de Madrid (UCM), Instituto de Investigación Sanitaria del Hospital Clínico San Carlos (IdISSC), Madrid, Spain | [e] Unidad de Gestión Clínica de Medicina Preventiva, Hospital Clínico San Carlos, Facultad de Enfermería, Universidad Complutense de Madrid (UCM), Instituto de Investigación Sanitaria del Hospital Clínico San Carlos (IdISSC), Madrid, Spain | [f] Departamento de Biología Molecular, Instituto de Salud Carlos III (ISCIII), Madrid, Spain

Correspondence: [*] Correspondence to: María José Gil Moreno, Hospital Universitario de Torrejón. Servicio de Neurología, Calle Mateo Inurria, s/n. 28850, Torrejón de Ardoz, Madrid, Spain. E-mail: [email protected].

Abstract: Frontotemporal lobar degeneration (FTLD) is a clinically, pathologically, and genetically heterogeneous group of disorders that affect the frontal and temporal lobes of the brain. FTLD classification distinguishes three main neuropathological groups: FTLD-tau, FTLD-TDP, and FTLD-FUS. As a four-repeat tauopathy, argyrophilic grain disease (AGD) is included in the FTLD-tau group. AGD may also appear in association with other neuropathological disorders. We describe the demographic, clinical, neuropathological, and genetic characteristics of a series of FTLD cases presenting with AGD. For this purpose, a clinico-pathological study of 71 autopsy-confirmed FTLD cases from different tissue banks was performed. AGD was found in 52.1% of FTLD cases. The presence of AGD increased with the increasing age (up to 88.9% in cases older than 80 years; p < 0.001) and was associated with higher ages at onset (p < 0.001) and death (p < 0.001). In AGD cases, progressive supranuclear palsy (PSP) was the most frequent clinical diagnosis (29.7%) and gait disturbance was the most common symptom (64.5%); behavioral and language symptoms were less frequent as compared with non-AGD cases (p = 0.055; p = 0.012). PSP was the most frequent neuropathological diagnosis among cases with AGD (32.4%). This group also showed less brain atrophy (p = 0.094) and higher prevalence of Alzheimer (p = 0.002) and vascular pathology (p = 0.047) as compared to the non-AGD group. We also observed that H1/H1 genotype was overrepresented in AGD cases (p = 0.018) and that there was no association with any specific APOE allele. A subanalysis of PSP cases according to the AGD status was carried out, yielding no significant differences.

Keywords: Argyrophilic grain disease, frontotemporal dementia, frontotemporal lobar degeneration, tauopathy

DOI: 10.3233/JAD-171115

Journal: Journal of Alzheimer's Disease, vol. 63, no. 3, pp. 1109-1117, 2018