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Limbic-predominant age-related TDP-43 encephalopathy (LATE) : consensus working group report

Nelson, Peter T. (författare)
Univ Kentucky, 311 Sanders Brown Ctr Aging, Lexington, KY 40536 USA
Dickson, Dennis W. (författare)
Mayo Clin, Jacksonville, FL 32224 USA
Trojanowski, John Q. (författare)
Univ Penn, Philadelphia, PA 19104 USA
visa fler...
Jack, Clifford R., Jr. (författare)
Mayo Clin, Rochester, MN USA
Boyle, Patricia A. (författare)
Rush Univ, Med Ctr, Chicago, IL 60612 USA
Arfanakis, Konstantinos (författare)
Rush Univ, Med Ctr, Chicago, IL 60612 USA;IIT, Chicago, IL 60616 USA
Rademakers, Rosa (författare)
Mayo Clin, Jacksonville, FL 32224 USA
Alafuzoff, Irina (författare)
Uppsala universitet,Klinisk och experimentell patologi
Attems, Johannes (författare)
Newcastle Univ, Newcastle Upon Tyne, Tyne & Wear, England
Brayne, Carol (författare)
Univ Cambridge, Cambridge, England
Coyle-Gilchrist, Ian T. S. (författare)
Univ Cambridge, Cambridge, England
Chui, Helena C. (författare)
Univ Southern Calif, Los Angeles, CA USA
Fardo, David W. (författare)
Univ Kentucky, 311 Sanders Brown Ctr Aging, Lexington, KY 40536 USA
Flanagan, Margaret E. (författare)
Univ Minnesota, Minneapolis, MN USA
Halliday, Glenda (författare)
Univ Sydney, Brain & Mind Ctr, Sydney, NSW, Australia;Cent Clin Sch, Fac Med & Hlth, Sydney, NSW, Australia
Hokkanen, Suvi R. K. (författare)
Univ Cambridge, Cambridge, England
Hunter, Sally (författare)
Univ Cambridge, Cambridge, England
Jicha, Gregory A. (författare)
Univ Kentucky, 311 Sanders Brown Ctr Aging, Lexington, KY 40536 USA
Katsumata, Yuriko (författare)
Univ Kentucky, 311 Sanders Brown Ctr Aging, Lexington, KY 40536 USA
Kawas, Claudia H. (författare)
Univ Calif Irvine, Irvine, CA USA
Keene, C. Dirk (författare)
Univ Washington, Seattle, WA 98195 USA
Kovacs, Gabor G. (författare)
Med Univ Vienna, Inst Neurol, Vienna, Austria
Kukull, Walter A. (författare)
Univ Washington, Seattle, WA 98195 USA
Levey, Allan I. (författare)
Emory Univ, Atlanta, GA 30322 USA
Makkinejad, Nazanin (författare)
IIT, Chicago, IL 60616 USA
Montine, Thomas J. (författare)
Stanford Univ, Stanford, CA 94305 USA
Murayama, Shigeo (författare)
Tokyo Metropolitan Geriatr Hosp, Tokyo, Japan;Inst Gerontol, Tokyo, Japan
Murray, Melissa E. (författare)
Mayo Clin, Jacksonville, FL 32224 USA
Nag, Sukriti (författare)
Rush Univ, Med Ctr, Chicago, IL 60612 USA
Rissman, Robert A. (författare)
Univ Calif San Diego, San Diego, CA 92103 USA;Harvard Univ, Cambridge, MA 02138 USA
Seeley, William W. (författare)
Univ Calif San Francisco, San Francisco, CA 94143 USA
Sperling, Reisa A. (författare)
White, Charles L., III (författare)
Univ Texas Southwestern Med Ctr Dallas, Dallas, TX 75390 USA
Yu, Lei (författare)
Rush Univ, Med Ctr, Chicago, IL 60612 USA
Schneider, Julie A. (författare)
Rush Univ, Med Ctr, Chicago, IL 60612 USA
visa färre...
 (creator_code:org_t)
2019
2019
Engelska.
Ingår i: Brain. - 0006-8950 .- 1460-2156. ; 142, s. 1503-1527
  • Forskningsöversikt (refereegranskat)
Abstract Ämnesord
Stäng  
  • We describe a recently recognized disease entity, limbic-predominant age-related TDP-43 encephalopathy (LATE). LATE neuropathological change (LATE-NC) is defined by a stereotypical TDP-43 proteinopathy in older adults, with or without coexisting hippocampal sclerosis pathology. LATE-NC is a common TDP-43 proteinopathy, associated with an amnestic dementia syndrome that mimicked Alzheimer's-type dementia in retrospective autopsy studies. LATE is distinguished from frontotemporal lobar degeneration with TDP-43 pathology based on its epidemiology (LATE generally affects older subjects), and relatively restricted neuroanatomical distribution of TDP-43 proteinopathy. In community-based autopsy cohorts, similar to 25% of brains had sufficient burden of LATE-NC to be associated with discernible cognitive impairment. Many subjects with LATE-NC have comorbid brain pathologies, often including amyloid-beta plaques and tauopathy. Given that the oldest-old' are at greatest risk for LATE-NC, and subjects of advanced age constitute a rapidly growing demographic group in many countries, LATE has an expanding but under-recognized impact on public health. For these reasons, a working group was convened to develop diagnostic criteria for LATE, aiming both to stimulate research and to promote awareness of this pathway to dementia. We report consensus-based recommendations including guidelines for diagnosis and staging of LATE-NC. For routine autopsy workup of LATE-NC, an anatomically-based preliminary staging scheme is proposed with TDP-43 immunohistochemistry on tissue from three brain areas, reflecting a hierarchical pattern of brain involvement: amygdala, hippocampus, and middle frontal gyrus. LATE-NC appears to affect the medial temporal lobe structures preferentially, but other areas also are impacted. Neuroimaging studies demonstrated that subjects with LATE-NC also had atrophy in the medial temporal lobes, frontal cortex, and other brain regions. Genetic studies have thus far indicated five genes with risk alleles for LATE-NC: GRN, TMEM106B, ABCC9, KCNMB2, and APOE. The discovery of these genetic risk variants indicate that LATE shares pathogenetic mechanisms with both frontotemporal lobar degeneration and Alzheimer's disease, but also suggests disease-specific underlying mechanisms. Large gaps remain in our understanding of LATE. For advances in prevention, diagnosis, and treatment, there is an urgent need for research focused on LATE, including in vitro and animal models. An obstacle to clinical progress is lack of diagnostic tools, such as biofluid or neuroimaging biomarkers, for ante-mortem detection of LATE. Development of a disease biomarker would augment observational studies seeking to further define the risk factors, natural history, and clinical features of LATE, as well as eventual subject recruitment for targeted therapies in clinical trials.

Ämnesord

MEDICAL AND HEALTH SCIENCES  -- Clinical Medicine -- Neurology (hsv//eng)
MEDICIN OCH HÄLSOVETENSKAP  -- Klinisk medicin -- Neurologi (hsv//swe)
MEDICAL AND HEALTH SCIENCES  -- Basic Medicine -- Neurosciences (hsv//eng)
MEDICIN OCH HÄLSOVETENSKAP  -- Medicinska och farmaceutiska grundvetenskaper -- Neurovetenskaper (hsv//swe)
MEDICIN OCH HÄLSOVETENSKAP  -- Medicinska och farmaceutiska grundvetenskaper (hsv//swe)
MEDICIN OCH HÄLSOVETENSKAP  -- Klinisk medicin (hsv//swe)
MEDICAL AND HEALTH SCIENCES  -- Basic Medicine (hsv//eng)
MEDICAL AND HEALTH SCIENCES  -- Clinical Medicine (hsv//eng)

Nyckelord

PET
MRI
FTLD
epidemiology
SNAP

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