Wolk David A, Nelson Peter T, Apostolova Liana, Arfanakis Konstantinos, Boyle Patricia A, Carlsson Cynthia M, Corriveau-Lecavalier Nick, Dacks Penny, Dickerson Bradford C, Domoto-Reilly Kimiko, Dugger Brittany N, Edelmayer Rebecca, Fardo David W, Grothe Michel J, Hohman Timothy J, Irwin David J, Jicha Gregory A, Jones David T, Kawas Claudia H, Lee Edward B, Lincoln Karen, Maestre Gladys E, Mormino Elizabeth C, Onyike Chiadi U, Petersen Ronald C, Rabinovici Gil D, Rademakers Rosa, Raman Rema, Rascovsky Katya, Rissman Robert A, Rogalski Emily, Scheltens Philip, Sperling Reisa A, Yang Hyun-Sik, Yu Lei, Zetterberg Henrik, Schneider Julie A
University of Pennsylvania, Philadelphia, Pennsylvania, USA.
University of Kentucky, Lexington, Kentucky, USA.
Alzheimers Dement. 2025 Jan;21(1):e14202. doi: 10.1002/alz.14202. Epub 2025 Jan 14.
Limbic predominant age-related TDP-43 encephalopathy neuropathologic change (LATE-NC) is highly prevalent in late life and a common co-pathology with Alzheimer's disease neuropathologic change (ADNC). LATE-NC is a slowly progressive, amnestic clinical syndrome. Alternatively, when present with ADNC, LATE-NC is associated with a more rapid course. With the emergence of anti-amyloid therapeutics, discrimination of LATE-NC from ADNC is critical and will lead to greater clinical recognition of amnestic patients without ADNC. Furthermore, co-pathology with LATE-NC may influence outcomes of these therapeutics. Thus there is a need to identify patients during life with likely LATE-NC. We propose criteria for clinical diagnosis of LATE as an initial framework for further validation. In the context of progressive memory loss and substantial hippocampal atrophy, criteria are laid out for probable (amyloid negative) or possible LATE (amyloid biomarkers are unavailable or when amyloid is present, but hippocampal neurodegeneration is out of proportion to expected pure ADNC). HIGHLIGHTS: Limbic-predominant age-related TDP-43 encephalopathy (LATE) is a highly prevalent driver of neuropathologic memory loss in late life. LATE neuropathologic change (LATE-NC) is a common co-pathology with Alzheimer's disease neuropathologic change (ADNC) and may influence outcomes with emerging disease-modifying medicines. We provide initial clinical criteria for diagnosing LATE during life either when LATE-NC is the likely primary driver of symptoms or when observed in conjunction with AD. Definitions of possible and probable LATE are provided.
边缘叶为主的年龄相关性TDP - 43脑病神经病理改变（LATE - NC）在老年人群中高度流行，是阿尔茨海默病神经病理改变（ADNC）常见的合并病理情况。LATE - NC是一种缓慢进展的遗忘性临床综合征。或者，当与ADNC同时存在时，LATE - NC会导致病程进展更快。随着抗淀粉样蛋白疗法的出现，区分LATE - NC与ADNC至关重要，这将使临床上对无ADNC的遗忘症患者有更深入的认识。此外，与LATE - NC的合并病理情况可能会影响这些疗法的效果。因此，有必要在生前识别可能患有LATE - NC的患者。我们提出了LATE临床诊断标准，作为进一步验证的初始框架。在进行性记忆丧失和海马体显著萎缩的背景下，制定了可能（淀粉样蛋白阴性）或疑似LATE（无法获得淀粉样蛋白生物标志物，或存在淀粉样蛋白但海马体神经退行性变与预期的单纯ADNC不成比例）的诊断标准。要点：边缘叶为主的年龄相关性TDP - 43脑病（LATE）是老年期神经病理性记忆丧失的高度流行原因。LATE神经病理改变（LATE - NC）是阿尔茨海默病神经病理改变（ADNC）常见的合并病理情况，可能会影响新型疾病修正药物的治疗效果。我们提供了在LATE - NC可能是症状的主要驱动因素或与AD同时出现时，生前诊断LATE的初步临床标准。给出了疑似和可能LATE的定义。
