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      Medial temporal lobe atrophy patterns in early- versus late-onset amnestic Alzheimer’s disease

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          Abstract

          Background:

          The medial temporal lobe (MTL) is hypothesized to be relatively spared in early-onset Alzheimer’s disease (EOAD). Yet, detailed examination of MTL subfield volumes and drivers of atrophy in amnestic EOAD is lacking.

          Methods:

          BioFINDER-2 participants with memory impairment, abnormal amyloid-β status and tau-PET were included. Forty-one EOAD individuals aged ≤65 years and, as comparison, late-onset AD (LOAD, ≥70 years, n=154) and Aβ-negative cognitively unimpaired controls were included. MTL subregions and biomarkers of (co-)pathologies were measured.

          Results:

          AD groups showed smaller MTL subregions compared to controls. Atrophy patterns were similar across AD groups, although LOAD showed thinner entorhinal cortices compared to EOAD. EOAD showed lower WMH compared to LOAD. No differences in MTL tau-PET or transactive response DNA binding protein 43-proxy positivity was found.

          Conclusions:

          We found in vivo evidence for MTL atrophy in amnestic EOAD and overall similar levels to LOAD of MTL tau pathology and co-pathologies.

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          Most cited references54

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          "Mini-mental state". A practical method for grading the cognitive state of patients for the clinician.

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            Neuropathological stageing of Alzheimer-related changes

            Eighty-three brains obtained at autopsy from nondemented and demented individuals were examined for extracellular amyloid deposits and intraneuronal neurofibrillary changes. The distribution pattern and packing density of amyloid deposits turned out to be of limited significance for differentiation of neuropathological stages. Neurofibrillary changes occurred in the form of neuritic plaques, neurofibrillary tangles and neuropil threads. The distribution of neuritic plaques varied widely not only within architectonic units but also from one individual to another. Neurofibrillary tangles and neuropil threads, in contrast, exhibited a characteristic distribution pattern permitting the differentiation of six stages. The first two stages were characterized by an either mild or severe alteration of the transentorhinal layer Pre-alpha (transentorhinal stages I-II). The two forms of limbic stages (stages III-IV) were marked by a conspicuous affection of layer Pre-alpha in both transentorhinal region and proper entorhinal cortex. In addition, there was mild involvement of the first Ammon's horn sector. The hallmark of the two isocortical stages (stages V-VI) was the destruction of virtually all isocortical association areas. The investigation showed that recognition of the six stages required qualitative evaluation of only a few key preparations.
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              VALIDITY OF THE TRAIL MAKING TEST AS AN INDICATOR OF ORGANIC BRAIN DAMAGE

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                Author and article information

                Journal
                bioRxiv
                BIORXIV
                bioRxiv
                Cold Spring Harbor Laboratory
                21 May 2024
                : 2024.05.21.594976
                Affiliations
                [1 ]Clinical Memory Research Unit, Department of Clinical Sciences Malmö, Lund University, 22242 Lund, Sweden
                [2 ]Department of Diagnostic Radiology, Clinical Sciences, Lund University, 22242 Lund, Sweden
                [3 ]Image and Function, Skåne University Hospital, 22242 Lund Sweden
                [4 ]Memory Clinic, Skåne University Hospital, 20502 Malmö, Sweden
                [5 ]Department of Neurology, Skåne University Hospital, 22242 Lund, Sweden
                [6 ]Wallenberg Center for Molecular Medicine, Lund University, 22184 Lund, Sweden
                [7 ]German Center for Neurodegenerative Diseases (DZNE), 39120 Magdeburg, Germany
                [8 ]Penn Image Computing and Science Laboratory (PICSL), Department of Radiology, University of Pennsylvania, Philadelphia 19104, USA
                Author notes
                [*]

                The authors contributed equally to this work.

                Nicola Spotorno and Laura E.M. Wisse share co-last/equal authorship.

                [# ]Correspondence to Laura E.M. Wisse or Anika Wuestefeld. Correspondence to: Laura Wisse, PhD, Department of Diagnostic Radiology, Lund University, Klinikgatan 13B, SE-222 42, Lund, Sweden, lemwisse@ 123456gmail.com , Anika Wuestefeld, MSc, Clinical Memory Research Unit, Department of Clinical Sciences Malmö, Lund University, Klinikgatan 28, Room C1103b, SE-222 42 Lund, Sweden, anika.wuestefeld@ 123456gmail.com
                Author information
                http://orcid.org/0000-0003-1779-3388
                http://orcid.org/0000-0001-5218-3337
                http://orcid.org/0000-0001-8649-9874
                http://orcid.org/0000-0002-0841-5580
                http://orcid.org/0000-0002-8885-7724
                http://orcid.org/0000-0003-2869-8378
                http://orcid.org/0000-0001-7147-0112
                http://orcid.org/0000-0002-9267-1930
                http://orcid.org/0000-0001-5503-6308
                http://orcid.org/0000-0003-1558-1883
                http://orcid.org/0000-0001-8543-4016
                http://orcid.org/0000-0001-8467-7286
                http://orcid.org/0000-0001-5404-8788
                http://orcid.org/0000-0001-7504-3943
                Article
                10.1101/2024.05.21.594976
                11142072
                38826333
                bc3b77ec-da0c-4d42-9f5c-e9721b60b984

                This work is licensed under a Creative Commons Attribution 4.0 International License, which allows reusers to distribute, remix, adapt, and build upon the material in any medium or format, so long as attribution is given to the creator. The license allows for commercial use.

                History
                Funding
                Funded by: MultiPark - A Strategic Research Area at Lund University
                Funded by: NIA
                Award ID: R01-AG070592
                Award ID: R01-AG069474
                Award ID: RF1-AG056014
                Funded by: Swedish Research Council
                Award ID: 2022-00900
                Funded by: Alzheimerfonden
                Award ID: AF980872
                Award ID: AF993465
                Funded by: Crafoord foundation
                Award ID: 20210690
                Funded by: European Research Council
                Award ID: ADG-101096455
                Funded by: Alzheimer’s Association
                Award ID: ZEN24-1069572
                Award ID: SG-23-1061717
                Funded by: GHR Foundation, Swedish Research Council
                Award ID: 2022-00775
                Award ID: 2018-02052
                Award ID: 2021-02219
                Funded by: ERA PerMed
                Award ID: ERAPERMED2021-184
                Funded by: Knut and Alice Wallenberg foundation
                Award ID: 2022-0231
                Funded by: Strategic Research Area MultiPark (Multidisciplinary Research in Parkinson’s disease) at Lund University, the Swedish Alzheimer Foundation
                Award ID: AF-980907
                Award ID: AF-980832
                Award ID: AF-994229
                Funded by: Swedish Brain Foundation
                Award ID: FO2021-0293
                Award ID: FO2022-0204
                Award ID: FO2023-0163
                Funded by: The Parkinson foundation of Sweden
                Award ID: 1412/22
                Funded by: Familjen Rönnströms Stiftelse
                Award ID: FRS-0003
                Funded by: WASP and DDLS Joint call
                Award ID: WASP/DDLS22-066
                Funded by: Cure Alzheimer’s fund, the Konung Gustaf V:s och Drottning Victorias Frimurarestiftelse, the Skåne University Hospital Foundation
                Award ID: 2020-O000028
                Funded by: Regionalt Forskningsstöd
                Award ID: 2022-1259
                Funded by: Swedish federal government
                Award ID: 2022-Projekt0280
                Award ID: 2022-Projekt0107
                Funded by: GE Healthcare
                Funded by: Fonds de recherche en Santé Québec
                Award ID: 298314
                Categories
                Article

                tau-pet imaging,amyloid-beta,mri,medial temporal lobe subregions,aging,in vivo,amnestic ad,early-onset,late-onset,amygdala segmentation protocol,tpd-43

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