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

J Alzheimers Dis. 2018;63(3):1109-1117. doi: 10.3233/JAD-171115.


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.

MeSH terms

  • Age Factors
  • Aged
  • Aged, 80 and over
  • Apolipoproteins E / genetics
  • Brain / metabolism
  • Brain / pathology*
  • DNA-Binding Proteins / metabolism
  • Female
  • Frontotemporal Lobar Degeneration / classification
  • Frontotemporal Lobar Degeneration / epidemiology
  • Frontotemporal Lobar Degeneration / genetics*
  • Frontotemporal Lobar Degeneration / pathology*
  • Humans
  • Male
  • Mutation / genetics*
  • Neurofibrillary Tangles / pathology
  • Neuropil / pathology*
  • RNA-Binding Protein FUS / metabolism
  • Retrospective Studies
  • tau Proteins / genetics*
  • tau Proteins / metabolism


  • Apolipoproteins E
  • DNA-Binding Proteins
  • FUS protein, human
  • RNA-Binding Protein FUS
  • TARDBP protein, human
  • tau Proteins