title: Incipient progressive supranuclear palsy is more common than expected and may comprise clinicopathological subtypes: a forensic autopsy series.
abstract: We investigated 998 serial Japanese forensic autopsy cases (0-101 years old, mean age 61.7 ± 21.9), with no case selection, using immunohistochemistry to detect cases with progressive supranuclear palsy (PSP). Twenty-nine cases (mean age 82.3 ± 7.2 years, 11 males, 18 females) fulfilled the National Institute of Neuronal Disorders and Stroke (NINDS)-PSP pathological criteria (2.9% of all cases, 4.6% of cases over 60). All had neuronal and glial inclusions in the basal ganglia and brainstem. However, 13 cases had low tau pathology and were categorized as atypical PSP. In addition to PSP pathology, multiple types of astrocytic inclusions and comorbid proteinopathies, particularly a high prevalence of argyrophilic grain disease, were found. All cases had not been diagnosed with PSP and had preserved daily functioning prior to death. However, 14 (48.3%), 11 (37.9%), and 16 (55.2%) cases showed signs of dementia, depressive state, and gait disturbance, respectively. Sixteen accidental death cases (55.2%), including from falls and getting lost, and 11 suicide cases (37.9%) appear to have a relationship with incipient PSP pathology. Cluster analysis using the distribution and amount of 4-repeat-tau pathology classified the cases into three subgroups: Group 1 (10 cases) had typical PSP pathology and seven cases (70.0%) had dementia as the most frequent symptom; Group 2 (7 cases) had significantly higher frequency of gait disorder (6 cases, 85.7%), and less neocortical tau pathology than Group 1; Group 3 (12 cases) had relatively mild PSP pathology and high argyrophilic grain burdens. Granular-shaped astrocytes were the dominant astrocytic inclusion in all cases. We conclude that in forensic cases incipient PSP occurs with a higher prevalence than expected. If these findings can be extrapolated to other population-based cohorts, PSP may be more common than previously thought.
authors.affiliation: Department of Neurology, Toyama University Hospital, Toyama, Japan.
authors.forename: Koji
authors.initials: K
authors.lastname: Yoshida
authors.affiliation: Department of Legal Medicine, Graduate School of Medicine and Pharmaceutical Sciences, University of Toyama, 2630 Sugitani, Toyama-shi, 930-0194 Toyama, Japan.
authors.forename: Yukiko
authors.initials: Y
authors.lastname: Hata
authors.affiliation: Department of Legal Medicine, Graduate School of Medicine and Pharmaceutical Sciences, University of Toyama, 2630 Sugitani, Toyama-shi, 930-0194 Toyama, Japan.
authors.forename: Koshi
authors.initials: K
authors.lastname: Kinoshita
authors.affiliation: Department of Neurology, Toyama University Hospital, Toyama, Japan.
authors.forename: Shutaro
authors.initials: S
authors.lastname: Takashima
authors.affiliation: Department of Neurology, Toyama University Hospital, Toyama, Japan.
authors.forename: Kortaro
authors.initials: K
authors.lastname: Tanaka
authors.affiliation: Department of Legal Medicine, Graduate School of Medicine and Pharmaceutical Sciences, University of Toyama, 2630 Sugitani, Toyama-shi, 930-0194 Toyama, Japan. nishida@med.u-toyama.ac.jp.
authors.forename: Naoki
authors.identifier: 0000-0002-6921-1768
authors.initials: N
authors.lastname: Nishida
mesh_terms: D000293:Adolescent; D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D001253:Astrocytes / Q000473:pathology; D001344:Autopsy; D001479:Basal Ganglia / Q000473:pathology*; D002648:Child; D002675:Child, Preschool; D005260:Female; D006801:Humans; D008297:Male; D008875:Middle Aged; D016874:Neurofibrillary Tangles / Q000473:pathology*; D010300:Parkinson Disease / Q000175:diagnosis / Q000473:pathology*; D013494:Supranuclear Palsy, Progressive / Q000175:diagnosis / Q000473:pathology*; D055815:Young Adult; D016875:tau Proteins / Q000378:metabolism
chemical_list: C054369:MAPT protein, human; D016875:tau Proteins
keywords: Astrocytes; Autopsy; Immunohistochemistry; Neuropathology; Progressive supranuclear palsy; Tauopathy