TY - JOUR
T1 - New insights into atypical Alzheimer's disease in the era of biomarkers
AU - Graff-Radford, Jonathan
AU - Yong, Keir X. X.
AU - Apostolova, Liana G.
AU - Bouwman, Femke H.
AU - Carrillo, Maria
AU - Dickerson, Bradford C.
AU - Rabinovici, Gil D.
AU - Schott, Jonathan M.
AU - Jones, David T.
AU - Murray, Melissa E.
N1 - Funding Information: This work was supported by National Institutes of Health (U01 AG057195 for LGA, MC, BCD, GDR, and MEM; and R01 AG054449 for JG-R and MEM). The funder had no role in the preparation of this Review. Funding Information: JG-R receives research funding from the National Institutes of Health (NIH) and serves as an assistant editor for Neurology. KXXY is funded by the Alzheimer's Society, grant number 453 (AS-JF-18–003). LGA served as a paid consultant for Biogen and receives research support from the NIH and the Alzheimer's Association. BCD receives research support from the NIH and Alzheimer's Drug Discovery Foundation; has been a paid consultant for Arkuda, Axovant, Lilly, Biogen, Merck, Novartis, and Wave LifeSciences; performs editorial duties with payment for Elsevier (Neuroimage: Clinical and Cortex); and receives royalties from Oxford University Press and Cambridge University Press. GDR receives research support from the NIH, Alzheimer's Association, American College of Radiology, Rainwater Charitable Foundation, Avid Radiopharmaceuticals, Eli Lilly, GE Healthcare, and Life Molecular Imaging; has been a paid consultant for Axon Neurosciences, Esiai, GE Healthcare, and Johnson & Johnson; and is an associate editor for JAMA Neurology. JMS acknowledges the support of the National Institute for Health Research University College London Hospitals Biomedical Research Centre, ARUK (ARUK-PG2017–1946), Weston Brain Institute (UB170045), Medical Research Council, and British Heart Foundation. He has received research funding and PET tracer from AVID Radiopharmaceuticals (a wholly owned subsidiary of Eli Lilly); has consulted for Roche, Eli Lilly, Biogen, Merck, and GE; received royalties from Oxford University Press and Henry Stewart Talks; given education lectures sponsored by Eli Lilly, Biogen, and GE; and served on a Data Safety Monitoring Committee for Axon Neuroscience. He is an associate editor for Alzheimer's Research and Therapy and Chief Medical Officer for Alzheimer's Research UK. DTJ receives research funding from the NIH. MEM receives funding from the NIH (R01 AG054449), Alzheimer's Association (AARG-17–533458), and the State of Florida (8az06, 20a22); and has served as a paid consultant for AVID Radiopharmaceuticals. All other authors declare no competing interests. Publisher Copyright: © 2021 Elsevier Ltd
PY - 2021/3/1
Y1 - 2021/3/1
N2 - Most patients with Alzheimer's disease present with amnestic problems; however, a substantial proportion, over-represented in young-onset cases, have atypical phenotypes including predominant visual, language, executive, behavioural, or motor dysfunction. In the past, these individuals often received a late diagnosis; however, availability of CSF and PET biomarkers of Alzheimer's disease pathologies and incorporation of atypical forms of Alzheimer's disease into new diagnostic criteria increasingly allows them to be more confidently diagnosed early in their illness. This early diagnosis in turn allows patients to be offered tailored information, appropriate care and support, and individualised treatment plans. These advances will provide improved access to clinical trials, which often exclude atypical phenotypes. Research into atypical Alzheimer's disease has revealed previously unrecognised neuropathological heterogeneity across the Alzheimer's disease spectrum. Neuroimaging, genetic, biomarker, and basic science studies are providing key insights into the factors that might drive selective vulnerability of differing brain networks, with potential mechanistic implications for understanding typical late-onset Alzheimer's disease.
AB - Most patients with Alzheimer's disease present with amnestic problems; however, a substantial proportion, over-represented in young-onset cases, have atypical phenotypes including predominant visual, language, executive, behavioural, or motor dysfunction. In the past, these individuals often received a late diagnosis; however, availability of CSF and PET biomarkers of Alzheimer's disease pathologies and incorporation of atypical forms of Alzheimer's disease into new diagnostic criteria increasingly allows them to be more confidently diagnosed early in their illness. This early diagnosis in turn allows patients to be offered tailored information, appropriate care and support, and individualised treatment plans. These advances will provide improved access to clinical trials, which often exclude atypical phenotypes. Research into atypical Alzheimer's disease has revealed previously unrecognised neuropathological heterogeneity across the Alzheimer's disease spectrum. Neuroimaging, genetic, biomarker, and basic science studies are providing key insights into the factors that might drive selective vulnerability of differing brain networks, with potential mechanistic implications for understanding typical late-onset Alzheimer's disease.
UR - http://www.scopus.com/inward/record.url?scp=85101442960&partnerID=8YFLogxK
U2 - https://doi.org/10.1016/S1474-4422(20)30440-3
DO - https://doi.org/10.1016/S1474-4422(20)30440-3
M3 - Review article
C2 - 33609479
SN - 1474-4422
VL - 20
SP - 222
EP - 234
JO - Lancet neurology
JF - Lancet neurology
IS - 3
ER -