Distinct Patterns of Hippocampal Pathology in Alzheimer's Disease with Transactive Response DNA-binding Protein 43.
Journal
Annals of neurology
ISSN: 1531-8249
Titre abrégé: Ann Neurol
Pays: United States
ID NLM: 7707449
Informations de publication
Date de publication:
Dec 2023
Dec 2023
Historique:
revised:
31
07
2023
received:
10
02
2023
accepted:
05
08
2023
medline:
16
11
2023
pubmed:
18
8
2023
entrez:
18
8
2023
Statut:
ppublish
Résumé
Age-related dementia syndromes are often not related to a single pathophysiological process, leading to multiple neuropathologies found at autopsy. An amnestic dementia syndrome can be associated with Alzheimer's disease (AD) with comorbid transactive response DNA-binding protein 43 (TDP-43) pathology (AD/TDP). Here, we investigated neuronal integrity and pathological burden of TDP-43 and tau, along the well-charted trisynaptic hippocampal circuit (dentate gyrus [DG], CA3, and CA1) in participants with amnestic dementia due to AD/TDP, amnestic dementia due to AD alone, or non-amnestic dementia due to TDP-43 proteinopathy associated with frontotemporal lobar degeneration (FTLD-TDP). A total of 48 extensively characterized cases (14 AD, 16 AD/TDP, 18 FTLD-TDP) were analyzed using digital HALO software (Indica Labs, Albuquerque, NM, USA) to quantify pathological burden and neuronal loss. In AD/TDP and FTLD-TDP, TDP-43 immunoreactivity was greatest in the DG. Tau immunoreactivity was significantly greater in DG and CA3 in AD/TDP compared with pure AD. All clinical groups showed the highest amounts of neurons in DG, followed by CA3, then CA1. The AD and AD/TDP groups showed lower neuronal counts compared with the FTLD-TDP group across all hippocampal subregions consistent with the salience of the amnestic phenotype. We conclude that AD/TDP can be distinguished from AD and FTLD-TDP based on differential regional distributions of hippocampal tau and TDP-43. Findings suggest that tau aggregation in AD/TDP might be enhanced by TDP-43. ANN NEUROL 2023;94:1036-1047.
Substances chimiques
DNA-Binding Proteins
0
tau Proteins
0
Types de publication
Journal Article
Langues
eng
Sous-ensembles de citation
IM
Pagination
1036-1047Subventions
Organisme : NIA NIH HHS
ID : K08AG065463
Pays : United States
Organisme : NIA NIH HHS
ID : R01AG062566
Pays : United States
Organisme : NIA NIH HHS
ID : F31 AG076318
Pays : United States
Organisme : NIA NIH HHS
ID : F31AG07631
Pays : United States
Organisme : NIA NIH HHS
ID : R01 AG077444
Pays : United States
Organisme : NIA NIH HHS
ID : P30AG072977
Pays : United States
Organisme : NINDS NIH HHS
ID : R01NS085770
Pays : United States
Organisme : NIA NIH HHS
ID : R01AG077444
Pays : United States
Organisme : NIA NIH HHS
ID : R56 AG075600
Pays : United States
Organisme : NIA NIH HHS
ID : R01 AG062566
Pays : United States
Organisme : NIA NIH HHS
ID : R56AG075600.
Pays : United States
Organisme : NINDS NIH HHS
ID : T32NS047987
Pays : United States
Informations de copyright
© 2023 The Authors. Annals of Neurology published by Wiley Periodicals LLC on behalf of American Neurological Association.
Références
Rabinovici GD, Carrillo MC, Forman M, et al. Multiple comorbid neuropathologies in the setting of Alzheimer's disease neuropathology and implications for drug development. Alzheimers Dement 2017;3:83-91.
Rahimi J, Kovacs GG. Prevalence of mixed pathologies in the aging brain. Alzheimers Res Ther 2014;6:82.
Uchino A, Takao M, Hatsuta H, et al. Incidence and extent of TDP-43 accumulation in aging human brain. Acta Neuropathol Commun 2015;20:35.
James BD, Wilson RS, Boyle PA, et al. TDP-43 stage, mixed pathologies, and clinical Alzheimer's-type dementia. Brain 2016;139:2983-2993.
Josephs KA, Whitwell JL, Weigand SD, et al. TDP-43 is a key player in the clinical features associated with Alzheimer's disease. Ann Neurol 2014;76:811-824.
Nelson PT, Dickson DW, Trojanowski JQ, et al. Limbic-predominant age-related TDP-43 encephalopathy (LATE): consensus working group report. Brain 2019;142:1503-1527.
Josephs KA, Murray ME, Tosakulwong N, et al. Pathological, imaging and genetic characteristics support the existence of distinct TDP-43 types in non-FTLD brains. Acta Neuropathol 2019;137:227-238.
Nag S, Yu L, Wilson RS, et al. TDP-43 pathology and memory impairment in elders without pathologic diagnoses of AD or FTLD. Neurology 2017;88:653-660.
Bejanin A, Schonhaut DR, La Joie R, et al. Tau pathology and neurodegeneration contribute to cognitive impairment in Alzheimer's disease. Brain 2017;140:3286-3300.
Jamshidi P, Kim G, Shahidehpour RK, et al. Distribution of TDP-43 pathology in hippocampal synaptic relays suggests transsynaptic propagation in frontotemporal lobar degeneration. J Neuropathol Exp Neurol 2020;79:585-591.
Albert MS, DeKosky ST, Dickson D, et al. The diagnosis of mild cognitive impairment due to Alzheimer's disease: recommendations from the National Institute on Aging-Alzheimer's Association workgroups on diagnostic guidelines for Alzheimer's disease. Alzheimers Dement 2011;7:270-279.
McKhann GM, Knopman DS, Chertkow H, et al. The diagnosis of dementia due to Alzheimer's disease: recommendations from the National Institute on Aging-Alzheimer's Association workgroups on diagnostic guidelines for Alzheimer's disease. Alzheimers Dement 2011;7:263-269.
Morris JC. The clinical dementia rating (CDR): current version and scoring rules. Neurology 1993;43:2412-2414.
Weintraub S, Salmon D, Mercaldo N, et al. The Alzheimer's disease Centers' uniform data set (UDS): the neuropsychologic test battery. Alzheimer Dis Assoc Disord 2009;23:91-101.
Wechsler D. Wechsler Memory Scale. 3rd ed. San Antonio, TX: The Psychological Corporation, 1997.
Mesulam M. Primary progressive aphasia: a dementia of the language network. Dement Neuropsychol 2013;7:2-9.
Rascovsky K, Hodges JR, Knopman D, et al. Sensitivity of revised diagnostic criteria for the behavioural variant of frontotemporal dementia. Brain 2011;134:2456-2477.
Mesulam M, Wicklund A, Johnson N, et al. Alzheimer and frontotemporal pathology in subsets of primary progressive aphasia. Ann Neurol 2008;63:709-719.
Irwin DJ, Cairns NJ, Grossman M, et al. Frontotemporal lobar degeneration: defining phenotypic diversity through personalized medicine. Acta Neuropathol 2015;129:469-491.
Irwin DJ, McMillan CT, Xie SX, et al. Asymmetry of post-mortem neuropathology in behavioural-variant frontotemporal dementia. Brain 2018;141:288-301.
Kwong LK, Neumann M, Sampathu DM, et al. TDP-43 proteinopathy: the neuropathology underlying major forms of sporadic and familial frontotemporal lobar degeneration and motor neuron disease. Acta Neuropathol 2007;114:63-70.
Gefen T, Mao Q, Kohler M, et al. Primary progressive aphasia has a unique signature distinct from dementia of the Alzheimer's type and behavioral variant frontotemporal dementia regardless of pathology. J Neuropathol Exp Neurol 2020;79:1379-1381.
Hyman BT, Phelps CH, Beach TG, et al. National Institute on Aging-Alzheimer's Association guidelines for the neuropathologic assessment of Alzheimer's disease. Alzheimers Dement 2012;8:1-13.
Montine TJ, Phelps CH, Beach TG, et al. National Institute on Aging-Alzheimer's Association guidelines for the neuropathologic assessment of Alzheimer's disease: a practical approach. Acta Neuropathol 2012;123:1-11.
Josephs KA, Murray ME, Whitwell JL, et al. Updated TDP-43 in Alzheimer's disease staging scheme. Acta Neuropathol 2016;131:571-585.
Mackenzie IR, Neumann M, Baborie A, et al. A harmonized classification system for FTLD-TDP pathology. Acta Neuropathol 2011;122:111-113.
Braak H, Braak E, Bohl J. Staging of Alzheimer-related cortical destruction. Eur Neurol 1993;33:403-408.
Lee EB, Porta S, Michael Baer G, et al. Expansion of the classification of FTLD-TDP: distinct pathology associated with rapidly progressive frontotemporal degeneration. Acta Neuropathol 2017;134:65-78.
Josephs KA, Murray ME, Whitwell JL, et al. Staging TDP-43 pathology in Alzheimer's disease. Acta Neuropathol 2014;127:441-450.
Nelson PT, Brayne C, Flanagan ME, et al. Frequency of LATE neuropathologic change across the spectrum of Alzheimer's disease neuropathology: combined data from 13 community-based or population-based autopsy cohorts. Acta Neuropathol 2022;144:27-44.
Fang YS, Tsai KJ, Chang YJ, et al. Full-length TDP-43 forms toxic amyloid oligomers that are present in frontotemporal lobar dementia-TDP patients. Nat Commun 2014;12:4824.
McAleese KE, Walker L, Erskine D, et al. TDP-43 pathology in Alzheimer's disease, dementia with Lewy bodies and ageing. Brain Pathol 2017;27:472-479.
Chen SD, Lu JY, Li HQ, et al. Staging tau pathology with tau PET in Alzheimer's disease: a longitudinal study. Transl Psychiatry 2021;11:483.
Guillozet AL, Weintraub S, Mash DC, Mesulam MM. Neurofibrillary tangles, amyloid, and memory in aging and mild cognitive impairment. Arch Neurol 2003;60:729-736.
Anderson P, Lomo T. Mode of activation of hippocampal pyramidal cells by excitatory synapses on dendrites. Exp Brain Res 1966;2:247-260.
Arnold SE, Hyman BT, Flory J, et al. The topographical and neuroanatomical distribution of neurofibrillary tangles and Neuritic plaques in the cerebral cortex of patients with Alzheimer's disease. Cereb Cortex 1991;1:103-116.
Stefanits H, Wesseling C, Kovacs GG. Loss of Calbindin immunoreactivity in the dentate gyrus distinguishes Alzheimer's disease from other neurodegenerative dementias. Neurosci Lett 2014;30:137-141.
Smith VD, Bachstetter AD, Ighodaro E, et al. Overlapping but distinct TDP-43 and tau pathologic patterns in aged hippocampi. Brain Pathol 2018;28:264-273.
Furcila D, Dominguez-Alvaro M, DeFelipe J, Alonso-Nanclares L. Subregional density of neurons, neurofibrillary tangles and amyloid plaques in the hippocampus of patients with Alzheimer's disease. Front Neuroanat 2019;13:99.
Chen-Plotkin AS, Lee VM, Trojanowski JQ. TAR DNA-binding protein 43 in neurodegenerative disease. Nat Rev Neurol 2010;6:211-220.
Montalbano M, McAllen S, Cascio FL, et al. TDP-43 and tau oligomers in Alzheimer's disease, amyotrophic lateral sclerosis, and frontotemporal dementia. Neurobiol Dis 2020;146:105130.
Higashi S, Watanabe R, Arai T. Fluorescence in-situ hybridization method reveals that carboxyl-terminal fragments of transactive response DNA-binding protein-43 truncated at the amino acid residue 218 reduce poly(A)+ RNA expression. Neuroreport 2018;29:846-851.
Jo M, Lee S, Jeon YM, et al. The role of TDP-43 propagation in neurodegenerative diseases: integrating insights from clinical and experimental studies. Exp Mol Med 2020;52:1652-1662.
Tong J, Huang C, Bi F, et al. Expression of ALS-linked TDP-43 mutant in astrocytes causes non-cell-autonomous motor neuron death in rats. EMBO J 2013;32:1917-1926.
Tome SO, Vandenberghe R, Ospitalieri S, et al. Distinct molecular patterns of TDP-43 pathology in Alzheimer's disease: relationship with clinical phenotypes. Acta Neuropathol Commun 2020;8:61.
Mao Q, Zheng X, Gefen T, et al. FTLD-TDP with and without GRN mutations cause different patterns of CA1 pathology. J Neuropathol Exp Neurol 2019;78:844-853.
Cairns NJ, Bigio EH, Mackenzie IR, et al. Neuropathologic diagnostic and nosologic criteria for frontotemporal lobar degeneration: consensus of the consortium for frontotemporal lobar degeneration. Acta Neuropathol 2007;114:5-22.
Connelly SJ, Mukaetova-Ladinska EB, Abdul-All Z, et al. Synaptic changes in frontotemporal lobar degeneration: correlation with MAPT haplotype and APOE genotype. Neuropathol Appl Neurobiol 2011;37:366-380.
Mackenzie IR, Baborie A, Pickering-Brown S, et al. Heterogeneity of ubiquitin pathology in frontotemporal lobar degeneration: classification and relation to clinical phenotype. Acta Neuropathol 2006;112:539-549.
Rosene DL, Van Hoesen GW. The hippocampal formation of the primate brain: a review of some comparative aspects of cytoarchitecture and connections. Cereb Cortex 1987;6:345-456.