Effects of the APOEɛ4 Allele on the Relationship Between Tau and Amyloid-β in Early- and Late-Onset Alzheimer’s Disease

Article type: Research Article

Authors: Kang, Jae Myeong^{a; 1} | Shin, Jeong-Hyeon^{b; c; 1} | Kim, Woo-Ram^d | Seo, Seongho^d | Seo, Haeun^d | Lee, Sang-Yoon^e | Park, Kee Hyung^f | Na, Duk L.^g | Okamura, Nobuyuki^h | Seong, Joon-Kyoung^{b; i; *} | Noh, Young^{f; j; *}

Affiliations: [a] Department of Psychiatry, Gil Medical Center, Gachon University College of Medicine, Incheon, Republic of Korea | [b] School of Biomedical Engineering, Korea University, Seoul, Republic of Korea | [c] Bio Medical Research Center, Bio Medical & Health Division, Korea Testing Laboratory, Daegu, Republic of Korea | [d] Neuroscience Research Institute, Gachon University, Incheon, Republic of Korea | [e] Department of Neuroscience, College of Medicine, Gachon University, Incheon, Republic of Korea | [f] Department of Neurology, Gil Medical Center, Gachon University College of Medicine, Incheon, Republic of Korea | [g] Department of Neurology, Samsung Medical Center, Sungkyunkwan University School of Medicine Seoul, Republic of Korea; Happymind Clinic, Seoul, Republic of Korea | [h] Division of Pharmacology, Faculty of Medicine, Tohoku Medical and Pharmaceutical University, Sendai, Japan | [i] Department of Artificial Intelligence, Korea University, Seoul, Republic of Korea | [j] Department of Health Science and Technology, GAIHST, Gachon University, Incheon, Republic of Korea

Correspondence: [*] Correspondence to: Young Noh, MD, PhD, Department of Neurology, Gil Medical Center, Gachon University College of Medicine, 21, 774-gil, Namdong-daero, Namdong-gu, Incheon 21565, Republic of Korea. Tel.: +82 32 460 3346; Fax: +82 32 460 3344; E-mail: [email protected] and Joon-Kyung Seong, PhD, Department of Artificial Intelligence, Korea University, 145, Anam-ro, Seongbuk-gu, Seoul 02841, Republic of Korea. Tel.: +82 2 3290 5660; E-mail: [email protected].

Note: [1] These authors contributed equally to this work.

Abstract: Background:Little is known regarding the differential effects of the apolipoprotein E (APOE) ɛ4 on the regional topography of amyloid and tau in patients with both early-onset (EOAD) and late-onset Alzheimer’s disease (LOAD). Objective:To compare the distribution and association of tau, amyloid, and cortical thickness among groups classified by the presence of APOE ɛ4 allele and onset age. Methods:A total of 165 participants including 54 EOAD patients (29 ɛ4-; 25 ɛ4+), 45 LOAD patients (21 ɛ4-; 24 ɛ4+), and 66 age-matched controls underwent 3T MRI, 18F-THK5351 (THK) and 18F-flutemetamol (FLUTE) PET scans, APOE genotyping, and neuropsychological tests. Data for voxel-wise and standardized uptake values from PET scans were analyzed in the context of APOE and age at onset. Results:EOAD ɛ4- patients showed greater THK retention in the association cortices, whereas their EOAD ɛ4+ counterparts had more retention in medial temporal areas. THK topography of LOAD ɛ4+ was similar to EOAD ɛ4 + . THK correlated positively with FLUTE and conversely with mean cortical thickness, being lowest in EOAD ɛ4-, highest in LOAD ɛ4-, and modest in ɛ4+ groups. Even in the APOE ɛ4+ groups, THK tended to correlate with FLUTE and mean cortical thickness in the inferior parietal region in EOAD and in the medial temporal region in LOAD. LOAD ɛ4- manifested with prevalent small vessel disease markers and the lowest correlation between THK retention and cognition. Conclusion:Our observations suggest the differential effects of the APOE ɛ4 on the relationship between tau and amyloid in EOAD and LOAD.

Keywords: Alzheimer’s disease, amyloid, APOE, early-onset Alzheimer’s disease, tau

DOI: 10.3233/JAD-230339

Journal: Journal of Alzheimer's Disease, vol. 94, no. 3, pp. 1233-1246, 2023