Tau and Amyloid-β Pathology in Japanese Forensic Autopsy Series Under 40 Years of Age: Prevalence and Association with APOE Genotype and Suicide Risk

Article type: Research Article

Authors: Yoshida, Koji^{a; b} | Hata, Yukiko^b | Ichimata, Shojiro^b | Nishida, Naoki^{b; *}

Affiliations: [a] Department of Neurology, Hyogo Brain and Heart Center, Hyogo, Japan | [b] Department of Legal Medicine, Graduate School of Medicine and Pharmaceutical Sciences, University of Toyama, Toyama, Japan

Correspondence: [*] Correspondence to: Naoki Nishida, Department of Legal Medicine, Graduate School of Medicine and Pharmaceutical Sciences, University of Toyama, 2630 Sugitani, Toyama 930-0194, Japan. Tel.: +81 76 434 7281; Fax: +81 76 434 5024; E-mail: [email protected].

Abstract: Background:Aggregation of abnormal phosphorylated tau in brain stem areas may be a possible early pathological manifestation of Alzheimer’s disease (AD). Objective:This study aimed to explore the prevalence of cases with AD-related pathology in subjects <40 years of age and to explore the association of such pathology, neuropsychiatric symptoms, and APOE genotype. Method:We conducted brain immunohistochemistry for 189 cases <40 years of age (mean±standard deviation age 25.3±13.1 years). Tau positive cases were then assessed for the distribution of tau pathology in the locus ceruleus (LC), raphe nucleus (RN), and entorhinal cortex (ErC), and the distinction between neuronal threads and cellular inclusions. Apolipoprotein E (APOE) genotype was also examined. Results:Tau pathology was detected in 135 cases (71.4%; 13–39 years; only LC, 23 cases; only RN, 4 cases; only ErC, 35 cases; LC+RN, 3 cases; LC+ErC, 57 cases; all three regions, 10 cases). The prevalence of thread pathology was higher than that of cellular inclusions. Significantly higher prevalence of the APOE ɛ2 allele were found in 10–39 years of age natural death cases (p < 0.05). Amyloid-β deposition was found in only 7 cases, along with a significantly high frequency of the ɛ4 allele (p < 0.05). While a past history of psychiatric disease was a significant risk factor for suicide, AD-related pathology was not associated with suicide. Conclusions:Both the brain stem and entorhinal cortex was the initial site of tau pathology in many younger subjects. AD-related pathology may not be a significant accelerating factor for suicide in younger subjects.

Keywords: Alzheimer’s disease, amyloid-β, APOE, neuropathology, suicide, tau

DOI: 10.3233/JAD-190196

Journal: Journal of Alzheimer's Disease, vol. 72, no. 2, pp. 641-652, 2019