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Evidence shows that LBD patients with AD copathology show an accelerated disease course, a greater risk of cognitive decline and an overall poorer prognosis. However, LBD-AD cases may show heterogeneous motor and non-motor phenotypes with a higher risk of dementia and, consequently, be not rarely misdiagnosed.<\/jats:p>\n               <jats:p>In this review, we summarize the current understanding of LBD-AD by discussing the synergistic effects of AD neuropathological changes and Lewy pathology and their clinical relevance. Furthermore, we provide an extensive overview of neuroimaging and fluid biomarkers under assessment for use in LBD-AD and their possible diagnostic and prognostic values. AD pathology can be predicted in vivo by means of CSF, MRI and PET markers, whereas the most promising technique to date for identifying Lewy pathology in different biological tissues is the \u03b1-synuclein seed amplification assay. Pathological imaging and CSF AD biomarkers are associated with a higher likelihood of cognitive decline in LBD but do not always mirror the neuropathological severity as in pure AD. Implementing the use of blood-based AD biomarkers might allow faster screening of LBD patients for AD copathology, thus improving the overall diagnostic sensitivity for LBD-AD.<\/jats:p>\n               <jats:p>Finally, we discuss the literature on novel candidate biomarkers being exploited in LBD-AD to investigate other aspects of neurodegeneration, such as neuroaxonal injury, glial activation and synaptic dysfunction. The thorough characterization of AD copathology in LBD should be taken into account when considering differential diagnoses of dementia syndromes, to allow prognostic evaluation on an individual level, and to guide symptomatic and disease-modifying therapies.<\/jats:p>","DOI":"10.1093\/brain\/awae203","type":"journal-article","created":{"date-parts":[[2024,7,11]],"date-time":"2024-07-11T19:26:39Z","timestamp":1720725999000},"page":"3325-3343","source":"Crossref","is-referenced-by-count":49,"title":["Clinical and diagnostic implications of Alzheimer's disease copathology in Lewy body disease"],"prefix":"10.1093","volume":"147","author":[{"ORCID":"https:\/\/orcid.org\/0000-0003-1328-3620","authenticated-orcid":false,"given":"Lorenzo","family":"Barba","sequence":"first","affiliation":[{"name":"Department of Neurology, Martin-Luther-University of Halle-Wittenberg , Halle 06120 ,","place":["Germany"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-0631-8506","authenticated-orcid":false,"given":"Samir","family":"Abu-Rumeileh","sequence":"additional","affiliation":[{"name":"Department of Neurology, Martin-Luther-University of Halle-Wittenberg , Halle 06120 ,","place":["Germany"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Henryk","family":"Barthel","sequence":"additional","affiliation":[{"name":"Department of Nuclear Medicine, University Hospital of Leipzig , Leipzig 04103 ,","place":["Germany"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Federico","family":"Massa","sequence":"additional","affiliation":[{"name":"Department of Neuroscience, Rehabilitation, Ophthalmology, Genetics, Maternal and Child Health, University of Genoa , Genoa 16132 ,","place":["Italy"]},{"name":"IRCCS Ospedale Policlinico San Martino , Genoa 16132 ,","place":["Italy"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Matteo","family":"Foschi","sequence":"additional","affiliation":[{"name":"Department of Biotechnological and Applied Clinical Sciences, University of L'Aquila , L'Aquila 67100 ,","place":["Italy"]},{"name":"Department of Neuroscience, Neurology Unit, S. Maria delle Croci Hospital of Ravenna, AUSL Romagna , Ravenna 48121 ,","place":["Italy"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Giovanni","family":"Bellomo","sequence":"additional","affiliation":[{"name":"Section of Neurology, Department of Medicine and Surgery, University of Perugia , Perugia 06129 ,","place":["Italy"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Lorenzo","family":"Gaetani","sequence":"additional","affiliation":[{"name":"Section of Neurology, Department of Medicine and Surgery, University of Perugia , Perugia 06129 ,","place":["Italy"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-1036-1075","authenticated-orcid":false,"given":"Dietmar R","family":"Thal","sequence":"additional","affiliation":[{"name":"Department of Imaging and Pathology, Laboratory for Neuropathology, Leuven Brain Institute, KU Leuven , Leuven 3001 ,","place":["Belgium"]},{"name":"Department of Pathology, UZ Leuven , Leuven 3000 ,","place":["Belgium"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Lucilla","family":"Parnetti","sequence":"additional","affiliation":[{"name":"Section of Neurology, Department of Medicine and Surgery, University of Perugia , Perugia 06129 ,","place":["Italy"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Markus","family":"Otto","sequence":"additional","affiliation":[{"name":"Department of Neurology, Martin-Luther-University of Halle-Wittenberg , Halle 06120 ,","place":["Germany"]}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"286","published-online":{"date-parts":[[2024,7,11]]},"reference":[{"key":"2024100318020000800_awae203-B1","doi-asserted-by":"crossref","first-page":"55","DOI":"10.1016\/S1474-4422(16)30291-5","article-title":"Neuropathological and genetic correlates of survival and dementia onset in synucleinopathies: A retrospective 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