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Relationships between Regional Neuronal Loss and Neurofibrillary Changes in the Hippocampal Formation and Duration and Severity of Alzheimer Disease
Abstract
The total numbers of neurons with and without neurofibrillary changes in the hippocampal subdivisions were estimated in 16 subjects with Alzheimer disease (AD) and in 5 normal elderly controls. On the basis of clinical symptoms, AD patients were subdivided into relatively less (AD-1. Functional Assessment Staging [FAST] stages 7a to 7c) and more severely affected (AD-2, FAST stages 7e to 7f) patient groups. In the AD-1 group relative to controls, the total number of neurons was reduced only in CA1 and in the subiculum. In the AD-2 group, neuronal losses were found in all sectors of the cornu Ammonis and in the subiculum and ranged from 53% in CA3 to 86% in CA1. The dentate gyrus was the only hippocampal subdivision without significant neuronal loss. Within the combined AD patient groups, significant correlations were noted between both clinical stage and duration of AD and both the total number of neurons and the percentage of neurons with neurofibrillary changes in CA1, CA4, and the subiculum. Regression analyses predicted neuronal losses over the maximal observed duration of 22 years of 87% in CA1, 63% in CA4, and 77% in the subiculum. Our data suggest that over the course of AD, continuous neurofibrillary tangle formation and continuous neuronal loss occur in the hippocampal subdivisions. The rate of neuronal loss appears to be similar for CA1, CA4, and the subiculum.
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“NFT depositions, on the other hand, damage neurons (45), favor the hippocampal formation over the neocortex in preclinical AD stages (3, 4), and may also be accelerated in E4 carriers (7).”
From Prediction of cognitive decline in normal elderly subjects with 2-[ 18 F]fluoro-2-deoxy- d -glucose/positron-emission tomography (FDG/PET) (2001) · cites this paper as [45]
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“In more advanced disease, the neuroanatomic distribution of NFTs correlates both with the location at which neurons die (302-305) and with the cognitive domains affected in patients with ADD.”
From Correlation of Alzheimer Disease Neuropathologic Changes With Cognitive Status: A Review of the Literature (2012) · cites this paper as [302]
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Self-citationNeuropathology and Cognitive Impairment in Alzheimer Disease: A Complex but Coherent Relationship
Nelson, P. T., Braak, H., & Markesbery, W. R. (2009) · Journal of Neuropathology & Experimental Neurology · doi:10.1097/nen.0b013e3181919a48 · Cited by 643
de Leon, M. J., Convit, A., Wolf, O. T., Tarshish, C. Y., DeSanti, S., Rusinek, H., Tsui, W., Kandil, E., Scherer, A. J., Roche, A., et al. (2001) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.191044198 · Cited by 629
Self-citationYushkevich, P. A., Pluta, J. B., Wang, H., Xie, L., Ding, S., Gertje, E. C., Mancuso, L., Kliot, D., Das, S. R., & Wolk, D. A. (2014) · Human Brain Mapping · doi:10.1002/hbm.22627 · Cited by 587
“An additional motivation for more granular measurement of MTL cortical subregions is that the PRC and ERC are amongst the earliest sites of neurodegeneration in AD [Braak and Braak, 1995; Bobinski et al., 1997; Simić et al., 1997; West et al., 2004].”
BackgroundBobinski, M., de Leon, M. J., Wegiel, J., DeSanti, S., Convit, A., Saint Louis, L. A., Rusinek, H., & Wisniewski✠, H. M. (1999) · Neuroscience · doi:10.1016/s0306-4522(99)00476-5 · Cited by 455
Self-citationReisberg, B., & Gauthier, S. (2007) · International Psychogeriatrics · doi:10.1017/s1041610207006412 · Cited by 338
Neuritic regeneration and synaptic reconstruction induced by withanolide A
Kuboyama, T., Tohda, C., & Komatsu, K. (2005) · British Journal of Pharmacology · doi:10.1038/sj.bjp.0706122 · Cited by 339
“…Group All rights reserved 0007–1188/05 $30.00 www.nature.com/bjp et al., 1994); amyloid b forms deposits in the brain, and subsequently induces neuronal cell death (Bobinski et al., 1997), neuritic atrophy (Canning et al., 1993; Knowles et al., 1999), and synaptic loss (Terry et al., 1991).”
BackgroundInfluentialBoekhoorn, K., Joëls, M., & Lucassen, P. J. (2006) · Neurobiology of Disease · doi:10.1016/j.nbd.2006.04.017 · Cited by 335
The pre-mild cognitive impairment, subjective cognitive impairment stage of Alzheimer’s disease.
Reisberg, B., Prichep, L., Mosconi, L., John, E. R., Glodzik‐Sobanska, L., Boksay, I., Monteiro, I., Torossian, C., Vedvyas, A., Ashraf, N., et al. (2008) · Alzheimer's & Dementia · doi:10.1016/j.jalz.2007.11.017 · Cited by 312
“[4] Bobinski M, Wegiel J, Tarnawski M, Bobinski M, Reisberg B, de”
BackgroundSubregional hippocampal atrophy predicts Alzheimer's dementia in the cognitively normal
Apostolova, L. G., Mosconi, L., Thompson, P. M., Green, A. E., Hwang, K., Ramírez, A., Mistur, R. L., Tsui, W. H., & de Leon, M. J. (2008) · Neurobiology of Aging · doi:10.1016/j.neurobiolaging.2008.08.008 · Cited by 327
“The subiculum and CA1 ere reported to be the most affected and CA3 and CA4 he least affected hippocampal subfields in post-mortem AD rains (Bobinski et al., 1995, 1997).”
BackgroundSelf-citationWright, A. L., Zinn, R., Hohensinn, B., Konen, L. M., Beynon, S. B., Tan, R. P., Clark, I. A., Abdipranoto, A., & Vissel, B. (2013) · PLoS ONE · doi:10.1371/journal.pone.0059586 · Cited by 322
BACE1 gene deletion prevents neuron loss and memory deficits in 5XFAD APP/PS1 transgenic mice
Ohno, M., Cole, S. L., Yasvoina, M., Zhao, J., Citron, M., Berry, R., Disterhoft, J. F., & Vassar, R. (2007) · Neurobiology of Disease · doi:10.1016/j.nbd.2006.12.008 · Cited by 290
“In this regard, it is interesting to note that neuron loss is also observed in both of these regions in AD brain (Bobinski et al., 1997;Giannakopoulos et al., 1996).”
BackgroundChanges in premorbid brain volume predict Alzheimer’s disease pathology
Silbert, L. C., Quinn, J. F., Moore, M. M., Corbridge, E., Ball, M. J., MURDOCH, G. H., Sexton, G. J., & Kaye, J. A. (2003) · Neurology · doi:10.1212/01.wnl.0000079053.77227.14 · Cited by 281
3D comparison of hippocampal atrophy in amnestic mild cognitive impairment and Alzheimer's disease
Apostolova, L. G., Dinov, I. D., Dutton, R. A., Hayashi, K. M., Toga, A. W., Cummings, J. L., & Thompson, P. M. (2006) · Brain · doi:10.1093/brain/awl274 · Cited by 251
Longitudinal CSF and MRI biomarkers improve the diagnosis of mild cognitive impairment
de Leon, M. J., DeSanti, S., Zinkowski, R. P., Mehta, P. D., Praticò, D., Segal, S., Rusinek, H., Li, J., Tsui, W., Louis, L. A. S., et al. (2005) · Neurobiology of Aging · doi:10.1016/j.neurobiolaging.2005.07.003 · Cited by 255
“comprised of hyperphosphorylated tau, neuronal loss and volume reductions [6,7,20].”
BackgroundSelf-citationNearly automatic segmentation of hippocampal subfields in in vivo focal T2-weighted MRI
Yushkevich, P. A., Wang, H., Pluta, J. B., Das, S. R., Craige, C. P., Avants, B., Weiner, M. W., & Mueller, S. G. (2010) · NeuroImage · doi:10.1016/j.neuroimage.2010.06.040 · Cited by 240
“…the extensive pathological evidence of heterogeneity in the way AD and other diseases affect the HF (Braak and Braak, 1991; Arnold et al., 1995; Bobinski et al., 1997; West et al., 2004; Duvernoy, 2005; Amaral and Lavenex, 2007), there is great interest in a robust HF subfield segmentation…”
Mosconi, L., De Santi, S., Brys, M., Tsui, W. H., Pirraglia, E., Glodzik-Sobanska, L., Rich, K. E., Switalski, R., Mehta, P. D., Pratico, D., et al. (2008) · Biological Psychiatry · doi:10.1016/j.biopsych.2007.05.030 · Cited by 238
Self-citationFailure of Neuronal Maturation in Alzheimer Disease Dentate Gyrus
Li, B., Yamamori, H., Tatebayashi, Y., Shafit-Zagardo, B., Tanimukai, H., Chen, S., Iqbal, K., & Grundke-Iqbal, I. (2008) · Journal of Neuropathology & Experimental Neurology · doi:10.1097/nen.0b013e318160c5db · Cited by 234
“The hippocampal formation, and especially the entorhinal cortex, CA1, and subiculum, are among the areas that are affected first and most severely in AD, whereas the granular layer of the dentate gyrus has generally been found to be spared (28, 31).”
BackgroundMRI and CSF studies in the early diagnosis of Alzheimer's disease
de Leon, M. J., DeSanti, S., Zinkowski, R. P., Mehta, P. D., Praticò, D., Segal, S., Clark, C. M., Kerkman, D. J., DeBernardis, J. F., Li, J., et al. (2004) · Journal of Internal Medicine · doi:10.1111/j.1365-2796.2004.01381.x · Cited by 226
Self-citationA critical discussion of the role of neuroimaging in mild cognitive impairment*
Wolf, H., Jelić, V., Gertz, H., Nordberg, A. K., Julin, P., & Wahlund, L. (2003) · Acta Neurologica Scandinavica · doi:10.1034/j.1600-0404.107.s179.10.x · Cited by 213
“Neuron loss in AD predilection areas was reported to be as high as 87% in subregions of the hippocampus (16) and up to 60% in the entorhinal cortex (17), even in early disease stages.”
BackgroundImaging the progression of Alzheimer pathology through the brain
Smith, A. D. (2002) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.082107399 · Cited by 202
Reisberg, ., Franssen, E., Souren, L. E. M., Auer, S., Akram, I., & Kenowsky, S. (2002) · American Journal of Alzheimer s Disease & Other Dementias® · doi:10.1177/153331750201700411 · Cited by 205
“These include hypoxia and beta-amyloid (1-42).”
Self-citationImaging and CSF Studies in the Preclinical Diagnosis of Alzheimer's Disease
de Leon, M. J., Mosconi, L., Blennow, K., DeSanti, S., Zinkowski, R. P., Mehta, P. D., Praticò, D., Tsui, W., Louis, L. A. S., Sobanska, L., et al. (2007) · Annals of the New York Academy of Sciences · doi:10.1196/annals.1379.012 · Cited by 200
Self-citationReisberg, ., Franssen, E., Hasan, S. M., Monteiro, I., Boksay, I., Souren, L. E. M., Kenowsky, S., Auer, S., Elahi, S., & Kluger, A. (1999) · European Archives of Psychiatry and Clinical Neuroscience · doi:10.1007/pl00014170 · Cited by 195
Self-citationCotman, C. W., & Head, E. (2008) · Journal of Alzheimer s Disease · doi:10.3233/jad-2008-15413 · Cited by 197
“Cortical atrophy, particularly in the hippocampus may result as a consequence of neuron loss, as report-ed in normal human brain aging [178,218] with more extensive losses occurring in AD [18,219].”
Kril, J., Patel, S., Harding, A., & Halliday, G. (2002) · Acta Neuropathologica · doi:10.1007/s00401-001-0477-5 · Cited by 190
“Our total estimate of CA1 neuron number in controls is less than some previous estimates (13.5 million [43], 14 million [61], 11.8 million [51], 13.5 million [ 6 ]), although similar to others (5.9 million [5]).”
ResultInfluentialYushkevich, P. A., Avants, B., Pluta, J. B., Das, S. R., Minkoff, D. L., Mechanic-Hamilton, D. J., Glynn, S. M., Pickup, S., LIU, W., & Gee, J. C. (2008) · NeuroImage · doi:10.1016/j.neuroimage.2008.08.042 · Cited by 178
“Non-uniform neuron loss across the hippocampal subfields has been reported in neurodegenerative disorders (West et al., 2004; Bobinski et al., 1997; Braak and Braak, 1991), as has a non-uniform rate of neuroplasticity (Eriksson et al., 1998; Kuhn et al., 1996; van Praag et al., 2002).”
Multimodality imaging characteristics of dementia with Lewy bodies
Kantarci, K., Lowe, V. J., Boeve, B. F., Weigand, S. D., Senjem, M. L., Przybelski, S. A., Dickson, D. W., Parisi, J. E., Knopman, D. S., Smith, G. E., et al. (2011) · Neurobiology of Aging · doi:10.1016/j.neurobiolaging.2011.09.024 · Cited by 178
Withanoside IV and its active metabolite, sominone, attenuate Aβ(25–35)‐induced neurodegeneration
Kuboyama, T., Tohda, C., & Komatsu, K. (2006) · European Journal of Neuroscience · doi:10.1111/j.1460-9568.2006.04664.x · Cited by 171
“present in two cortical regions (parietal cortex and temporal cortex) and in two hippocampal regions (CA1 and CA3) in patients with Alzheimer’s disease (DeKosky & Scheff, 1990; Bobinski et al., 1997) and in mouse models of Alzheimer’s disease (Games et al.”
BackgroundInfluentialAbnormalities of hippocampal surface structure in very mild dementia of the Alzheimer type
Wang, L., Miller, J. P., Gado, M. H., McKeel, D. W., Rothermich, M. A., Miller, M. I., Morris, J. C., & Csernansky, J. G. (2005) · NeuroImage · doi:10.1016/j.neuroimage.2005.09.017 · Cited by 171
“…deformation found to discriminate the DAT subjects from the healthy nondemented subjects is consistent with the pattern of neuropathological findings found within the hippocampus (Bobinski et al., 1998, 1997; Mizukami et al., 1998; Muramori et al., 1998; Price and Morris, 1999; Sheng et al., 1998).”
BackgroundResultStage-dependent and sector-specific neuronal loss in hippocampus during Alzheimer's disease
Rössler, M., Zarski, R., Bohl, J., & Ohm, T. (2002) · Acta Neuropathologica · doi:10.1007/s00401-001-0475-7 · Cited by 164
“With regard to the distribution of AD-associated neuronal loss, our results agree with those published by West et al. [11], who reported a sector-specific loss in CA1 and the subiculum, and Bobinski et al. [ 9 ], who described a significant loss of neurons in the subiculum and sector CA1 of patients clinically staged…”
BackgroundResultInfluentialIvins, K. J., Bui, E. T. N., & Cotman, C. W. (1998) · Neurobiology of Disease · doi:10.1006/nbdi.1998.0228 · Cited by 164
“Moreover, a profound loss of neurons is an invariant feature of AD (Bobinski et al., 1997; Gomez-Isla et al., 1996).”
BackgroundThal, D. R., Holzer, M., Rüb, U., Waldmann, G., Günzel, S., Zedlick, D., & Schober, R. (2000) · Experimental Neurology · doi:10.1006/exnr.2000.7380 · Cited by 165
A canine model of human aging and Alzheimer's disease
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Kantarci, K., Weigand, S. D., Przybelski, S. A., Shiung, M. M., Whitwell, J. L., Negash, S., Knopman, D. S., Boeve, B. F., O’Brien, P. C., Petersen, R. C., et al. (2009) · Neurology · doi:10.1212/wnl.0b013e3181a2e864 · Cited by 160
Youssef, S. A., Capucchio, M. T., Rofina, J., CHAMBERS, J. K., Uchida, K., Nakayama, H., & Head, E. (2016) · Veterinary Pathology · doi:10.1177/0300985815623997 · Cited by 166
“The neurobiological basis for brain atrophy may be due to a loss of neurons or potentially shrinking of neurons (ie, changes in density) as observed in normal brain aging and more extensively in AD in people.(13,167,206) Scoring or evaluating neuronal loss in sections stained with hematoxylin and eosin is challenging…”
Good, P. F., Alapat, D. V., Hsu, A., Chu, C., Perl, D. P., Wen, X., Burstein, D., & Kohtz, D. S. (2004) · Journal of Neurochemistry · doi:10.1111/j.1471-4159.2004.02766.x · Cited by 150
“Additionally, we have demonstrated that CA3 neurons lack phosphorylated MAP1B in all but the advanced AD cases where CA3 neurons are lost as well (Bobinski et al. 1997).”
BackgroundThe Alzheimer's Disease Activities of Daily Living International Scale (ADL-ISY)
Reisberg, ., Finkel, S. I., Overall, J. E., et al. (2001) · International Psychogeriatrics · doi:10.1017/s1041610201007566 · Cited by 148
Self-citationHippocampal subfield volumetry from structural isotropic 1 mm3 MRI scans: A note of caution
Wisse, L. E. M., Chételat, G., Daugherty, A. M., de Florès, R., Joie, R. L., Mueller, S. G., Stark, C. E. L., Wang, L., Yushkevich, P. A., Berron, D., et al. (2020) · Human Brain Mapping · doi:10.1002/hbm.25234 · Cited by 137
“pathology (Braak & Braak, 1991), which is closely related to neurodegeneration (Bobinski et al., 1997; Fukutani et al., 1995), the earliest and strongest volume loss is expected in CA1, then the subiculum, while the other CA regions and the dentate”
Background1H Magnetic resonance spectroscopy in dementia
Kantarci, K. (2007) · British Journal of Radiology · doi:10.1259/bjr/60346217 · Cited by 136
3D PIB and CSF biomarker associations with hippocampal atrophy in ADNI subjects
Apostolova, L. G., Hwang, K., Andrawis, J. P., Green, A. E., Babakchanian, S., Morra, J. H., Cummings, J. L., Toga, A. W., Trojanowski, J. Q., Shaw, L. M. J., et al. (2010) · Neurobiology of Aging · doi:10.1016/j.neurobiolaging.2010.05.003 · Cited by 144
Contribution of Structural Neuroimaging to the Early Diagnosis of Alzheimer’s Disease
de Leon, M. J., Convit, A. J., DeSanti, S., Carroll, R., GEORGE, A. E., Rusinek, H., Bobinski, M., Wı́sniewski, H. M., & Louis, L. A. S. (1997) · International Psychogeriatrics · doi:10.1017/s1041610297004900 · Cited by 135
“More specifically the entorhinal cortex, the subiculum, and the CAI of the hippocampus are the sites of the most extensive quantitative pathology (Bobinski et al., 1997).”
BackgroundSelf-citationTau and Axonopathy in Neurodegenerative Disorders
Higuchi, M., Lee, V. M.-Y., & Trojanowski, J. Q. (2002) · NeuroMolecular Medicine · doi:10.1385/nmm:2:2:131 · Cited by 134
“…neurons (McKee et al., 1991; Arriagada et al., 1992; Bancher et al., 1993; 1996; Dickson et al., 1992; Hyman et al., 1995; GomezIsla et al., 1996; Bobinski et al, 1997; Thal et al., 1998; Neve and Robakis, 1998), indicating that the intraneuronal accumulation of fibrillary tau is one of the…”
Bobinski, M., de Leon, M. J., Tarnawski, M. J., Węgiel, J., Bobinski, M., Reisberg, ., Miller, D. C., & Wı́sniewski, H. M. (1998) · Brain Research · doi:10.1016/s0006-8993(98)00759-8 · Cited by 129
Self-citationVariations in the neuropathology of familial Alzheimer’s disease
Shepherd, C. E., McCann, H., & Halliday, G. M. (2009) · Acta Neuropathologica · doi:10.1007/s00401-009-0521-4 · Cited by 135
Xie, L., Wisse, L. E. M., Pluta, J. B., de Florès, R., Piskin, V., Manjón, J. V., Wang, H., Das, S. R., Ding, S., Wolk, D. A., et al. (2019) · Human Brain Mapping · doi:10.1002/hbm.24607 · Cited by 120
“As NFT pathology is closely related to neuron and synapse loss (Bobinski et al., 1997; Braak & Braak, 1991; Fukutani et al., 1995), certain MTL subregions may therefore show early and selective atrophy and serve as imaging biomarker in the early stages of AD.”
Variation in hippocampal neuron number with age and brain volume
Harding, A. (1998) · Cerebral Cortex · doi:10.1093/cercor/8.8.710 · Cited by 120
“With the development of more sophisticated and sensitive imaging techniques, brain atrophy, and in particular hippocampal atrophy, is being used to identify early Alzheimer's disease (Jobst et al., 1994; Bobinski et al., 1997).”
BackgroundMethodMild cognitive impairment (MCI): a historical perspective
Reisberg, ., Ferris, S. H., Kluger, A., Franssen, E., Węgiel, J., & de Leon, M. J. (2007) · International Psychogeriatrics · doi:10.1017/s1041610207006394 · Cited by 126
Self-citationHippocampal Subfield Volumetry and 3D Surface Mapping in Subjective Cognitive Decline
Perrotin, A., de Flores, R., Lamberton, F., Poisnel, G., La Joie, R., de la Sayette, V., Mézenge, F., Tomadesso, C., Landeau, B., Desgranges, B., et al. (2015) · Journal of Alzheimer's Disease · doi:10.3233/jad-150087 · Cited by 119
Mathieu-Kia, A.-M., Fan, L.-Q., Kreek, M. J., Simon, E. J., & Hiller, J. M. (2001) · Brain Research · doi:10.1016/s0006-8993(00)03302-3 · Cited by 118
Mouse Models of Alzheimer's Disease: Insight into Treatment
German, D. C., & Eisch, A. J. (2004) · Reviews in the Neurosciences · doi:10.1515/revneuro.2004.15.5.353 · Cited by 114
Barnes, J., Foster, J., Boyes, R. G., Pepple, T., Moore, E. K., Schott, J. M., Frost, C. D., Scahill, R. I., & Fox, N. C. (2008) · NeuroImage · doi:10.1016/j.neuroimage.2008.01.012 · Cited by 115
“Autopsy studies have shown the hippocampus to be affected by Alzheimer’s disease pathology early in the disease process, with approximately 20–50% loss of neurons by the time individuals are moderately affected (Bobinski et al., 1997; Braak and Braak, 1991).”
BackgroundMicroRNA in Alzheimer’s disease: an exploratory study in brain, cerebrospinal fluid and plasma
Bekris, L. M., Lutz, F., Montine, T. J., Yu, C. E., Tsuang, D., Peskind, E. R., & Leverenz, J. B. (2013) · Biomarkers · doi:10.3109/1354750x.2013.814073 · Cited by 97
“Previous study suggests that CB shows very little, if any AD-related pathology in end-stage AD, compared to HP (Bobinski et al., 1997; Fukutani et al., 1995; Rossler et al., 2002).”
ResultDendritic changes in Alzheimer's disease and factors that may underlie these changes
Anderton, B. H., Callahan, L. M., Coleman, P. D., Davies, P., Flood, D. G., Jicha, G. A., Ohm, T. G., & Weaver, C. L. (1998) · Progress in Neurobiology · doi:10.1016/s0301-0082(98)00022-7 · Cited by 113
“In addition, recent study has provided information on ageing and Alzheimer-related excess neuronal loss in selected subdivisions of the hippocampus (West, 1993; West et al., 1994; Bobinski et al., 1997; Simic et al., 1997) and in the entorhinal cortex (Gomez Isla et al., 1996).”
Pluta, J., Yushkevich, P., Das, S., & Wolk, D. (2012) · Journal of Alzheimer's Disease · doi:10.3233/jad-2012-111931 · Cited by 107
“pal neurodegeneration [22–24, 26].”
Parra, M. A., Sala, S. D., Abrahams, S., Logie, R. H., Méndez, L., & Lopera, F. J. (2011) · Neuropsychologia · doi:10.1016/j.neuropsychologia.2011.03.022 · Cited by 112
“These deficits are expressed clinically when substantial neuronal loss has occurred (Bobinski et al., 1997; Velez et al., 2004; West, Coleman, Flood, & Troncoso, 1995).”
Background3D comparison of low, intermediate, and advanced hippocampal atrophy in MCI
Apostolova, L. G., Thompson, P. M., Green, A. E., Hwang, K., Zoumalan, C., Jack, C. R., Harvey, D. J., Petersen, R. C., Thal, L. J., Aisen, P. S. S., et al. (2010) · Human Brain Mapping · doi:10.1002/hbm.20905 · Cited by 100
“Subfields CA2–4 are involved relatively later and show lesser neurofibrillary pathology across the disease spectrum [Bobinski et al., 1995, 1997; Schonheit et al., 2004].”
Global measures: utility in defining and measuring treatment response in dementia
Reisberg, . (2007) · International Psychogeriatrics · doi:10.1017/s1041610207005261 · Cited by 101
Self-citationA Monoclonal Antibody to Amyloid Precursor Protein Induces Neuronal Apoptosis
Rohn, T. T., Ivins, K. J., Bahr, B. A., Cotman, C. W., & Cribbs, D. H. (2000) · Journal of Neurochemistry · doi:10.1046/j.1471-4159.2000.0742331.x · Cited by 98
“These results highlight a novel function for normal APP and suggest that inappropriate clustering of APP on the plasma membrane of neurons may be a contributing factor in the profound loss of neurons associated with AD (Bobinski et al., 1997).”
BackgroundSheffield, L. G., Marquis, J. G., & Berman, N. E. J. (2000) · Neuroscience Letters · doi:10.1016/s0304-3940(00)01037-5 · Cited by 96
Three-dimensional mapping of neurofibrillary tangle burden in the human medial temporal lobe
Yushkevich, P. A., Muñoz, M., Martin, M. M. I. D. O., Ittyerah, R., Lim, S., Ravikumar, S., Bedard, M. L., Pickup, S., Liu, W., Wang, J., et al. (2021) · Brain · doi:10.1093/brain/awab262 · Cited by 96
“Tau neurofibrillary tangle (NFT) pathology is closely linked to neurodegeneration and cognitive decline in Alzheimer’s disease.(1) The topographic characterization of the spread of NFT pathology through the human brain by Braak and others has had tremendous impact in many areas of Alzheimer’s disease research, includi…”
BackgroundWęgiel, J., Kuchna, I., Nowicki, K., Frackowiak, J., Mazur‐Kolecka, B., Imaki, H., Wegiel, J., Mehta, P. D., Silverman, W. P., Reisberg, ., et al. (2007) · Acta Neuropathologica · doi:10.1007/s00401-006-0191-4 · Cited by 89
“In the memory systems of persons with DS/AD or sporadic AD, neuroWbrillary degeneration is the major cause of neuronal loss and, therefore, the major factor contributing to the reduction of intraneuronal A. Over the course of 22 years, an AD patient loses 87% of the neurons in the CA1 and 63% in the CA4 sector, and 77…”
BackgroundSelf-citationMuramori, F., Kobayashi, K., & Nakamura, I. (1998) · Psychiatry and Clinical Neurosciences · doi:10.1111/j.1440-1819.1998.tb02706.x · Cited by 86
Aging in the Canine and Feline Brain
Vite, C. H., & Head, E. (2014) · Veterinary Clinics of North America Small Animal Practice · doi:10.1016/j.cvsm.2014.07.008 · Cited by 103
de Vargas, D. M., Bastiani, M. A. D., Zimmer, E. R., & Klamt, F. (2018) · Alzheimer s Research & Therapy · doi:10.1186/s13195-018-0394-7 · Cited by 91
“A reduction in the neuronal population is directly related to the progression of hippocampal atrophy, to the severity of the dementia [69, 70], and to the Braak stage of the disease [71].”
BackgroundCombs, B., Hamel, C., & Kanaan, N. M. (2016) · Neurobiology of Disease · doi:10.1016/j.nbd.2016.05.016 · Cited by 93
Bronfman, F. C., Moechars, D., & LEUVEN, F. V. (2000) · Neurobiology of Disease · doi:10.1006/nbdi.2000.0283 · Cited by 86
Kantarci, K., Petersen, R. C., Przybelski, S. A., Weigand, S. D., Shiung, M. M., Whitwell, J. L., Negash, S., Ivnik, R. J., Boeve, B. F., Knopman, D. S., et al. (2008) · Archives of Neurology · doi:10.1001/archneur.65.12.1621 · Cited by 84
“(%) of subjects with any cortical infarctions 0 6 (7) 5 (16) 3 (15) .”
Apostolova, L. G., Morra, J. H., Green, A. E., Hwang, K., Avedissian, C., Woo, E., Cummings, J. L., Toga, A. W., Jack, C. R., Weiner, M. W., et al. (2010) · NeuroImage · doi:10.1016/j.neuroimage.2009.12.125 · Cited by 87
“It is one of the first regions to be affected and throughout the disease course consistently shows the highest pathology burden (Bobinski et al., 1997, 1995; Schonheit et al., 2004; Zarow et al., 2005).”
Unraveling the complexity of human brain: Structure, function in healthy and disease states
Sultana, O. F., Bandaru, M., Islam, M. A., & Reddy, P. H. (2024) · Ageing Research Reviews · doi:10.1016/j.arr.2024.102414 · Cited by 92
Sabbagh, M. N., Cooper, K., DeLange, J., Stoehr, J. D., Thind, K., Lahti, T., Reisberg, B., Sue, L., Vedders, L., Fleming, S. R., et al. (2010) · Current Alzheimer Research · doi:10.2174/156720510791162340 · Cited by 79
“Another study addressed neuronal loss and neurofibrillary changes [11] In that study, significant correlations were noted between the FAST and the total number of neurons and the percentage of neurons with neurofibrillary changes in CA1, CA4, and the subiculum.”
BackgroundThe dentate gyrus in Alzheimer's disease
Ohm, T. G. (2007) · Progress in brain research · doi:10.1016/s0079-6123(07)63039-8 · Cited by 78
Hall, G. F., Chu, B., Lee, G. S., & Yao, J. (2000) · Journal of Cell Science · doi:10.1242/jcs.113.8.1373 · Cited by 78
Proton MRS in mild cognitive impairment
Kantarci, K. (2013) · Journal of Magnetic Resonance Imaging · doi:10.1002/jmri.23800 · Cited by 76
Head, E. (2010) · AGE · doi:10.1007/s11357-010-9183-3 · Cited by 81
Velez‐Pardo, C., Arellano, J. I., Cardona‐Gómez, G. P., Jiménez-Del-Río, M., Lopera, F. J., & DeFelipe, J. (2004) · Epilepsia · doi:10.1111/j.0013-9580.2004.55403.x · Cited by 72
“(15) found a profound loss of neurons (86%) in the CA1 sector, and it also appears to show a unique relation with clinical measures of AD (16).”
BackgroundHagihara, H., Murano, T., Ohira, K., Miwa, M., Nakamura, K., & Miyakawa, T. (2019) · Molecular Brain · doi:10.1186/s13041-019-0522-8 · Cited by 70
Wu, G., Sankaranarayanan, S., Wong, J., Tugusheva, K., Michener, M. S., Shi, X., Cook, J. J., Simon, A. J., & Savage, M. J. (2012) · Journal of Neuroscience Research · doi:10.1002/jnr.23122 · Cited by 68
“Many reports have demonstrated a decline in CSF Ab42 and elevation of total tau, ptau, and tau/Ab42 ratio in AD subjects, and these markers show temporal changes with disease progression and in early or prodromal stages of the disease (Bobinski et al., 1997; Mulder et al., 2010; Sonnenna et al., 2010; De Meyer et al.,…”
Supporting Family Caregivers With Technology for Dementia Home Care: A Randomized Controlled Trial
Williams, K. N., Perkhounkova, Y., Shaw, C. A., Hein, M., Vidoni, E. D., & Coleman, C. (2019) · Innovation in Aging · doi:10.1093/geroni/igz037 · Cited by 71
Kril, J. J., Hodges, J. R., & Halliday, G. M. (2004) · Neuroscience Letters · doi:10.1016/j.neulet.2004.02.001 · Cited by 72
Tang, X., Qin, Y., Wu, J., Zhang, M., Zhu, W., & Miller, M. I. (2016) · Magnetic Resonance Imaging · doi:10.1016/j.mri.2016.05.001 · Cited by 64
“Our observed CA2 atrophy of the hippocampus has also been reported in a range of previous publications [15, 20, 62, 65-68].”
Reisberg, ., Kenowsky, S., Franssen, E., et al. (1999) · International Psychogeriatrics · doi:10.1017/s1041610299005554 · Cited by 65
Self-citationTang, X., Holland, D., Dale, A. M., Laurent Younes, B., Miller, M. I., & Initiative, A. D. N. (2015) · Human Brain Mapping · doi:10.1002/hbm.22758 · Cited by 67
“Indeed, there has been evidence showing that the neuropathological changes that occur in Alzheimer dementia cause neuronal loss in the hippocampus [Price et al., 2001], with a resultant volume reduction over time [Bobinski et al., 1996].”
BackgroundLiu, A. K. L., Chau, T. W., Lim, E., Ahmed, I., Chang, R. C., Kalaitzakis, M. E., Graeber, M. B., Gentleman, S., & Pearce, R. K. B. (2019) · Acta Neuropathologica Communications · doi:10.1186/s40478-019-0717-3 · Cited by 64
Early marker for Alzheimer's disease: Hippocampus T1rho (T 1ρ ) estimation
Haris, M., McArdle, E. L., Fenty, M., Singh, A. K., Davatzikos, C. A., Trojanowski, J. Q., Melhem, E. R., Clark, C. M., & Borthakur, A. (2009) · Journal of Magnetic Resonance Imaging · doi:10.1002/jmri.21735 · Cited by 64
“Autopsy studies have shown the hippocampus to be affected by AD pathology early in the disease process, with 20%– 50% loss of neurons by the time individuals are moderately affected (2,3).”
BackgroundReisberg, ., Monteiro, I. M., Torossian, C. L., Auer, S., Shulman, M. B., Ghimire, S., Boksay, I., Guillo‐Benarous, F., Osorio, R. S., Vengassery, A., et al. (2014) · Dementia and Geriatric Cognitive Disorders · doi:10.1159/000357839 · Cited by 67
Self-citationNaito, R., & Tohda, C. (2006) · Biological and Pharmaceutical Bulletin · doi:10.1248/bpb.29.1892 · Cited by 61
Pearson, A. G., Curtis, M. A., Waldvogel, H. J., Faull, R. L. M., & Dragunow, M. (2005) · Neuroscience · doi:10.1016/j.neuroscience.2005.02.029 · Cited by 63
Tangles, Toxicity, and Tau Secretion in AD – New Approaches to a Vexing Problem
Gendreau, K. L., & Hall, G. F. (2013) · Frontiers in Neurology · doi:10.3389/fneur.2013.00160 · Cited by 67
Impaired spatial memory in APP-overexpressing mice on a homocysteinemia-inducing diet
Bernardo, A., McCord, M. C., Troen, A. M., Allison, J. D., & McDonald, M. P. (2006) · Neurobiology of Aging · doi:10.1016/j.neurobiolaging.2006.05.035 · Cited by 59
Bai, Y., Tohda, C., Zhu, S., Hattori, M., & Komatsu, K. (2011) · Journal of Natural Medicines · doi:10.1007/s11418-011-0509-y · Cited by 58
“In AD, neuritic atrophy and synaptic loss occur prior to the neuronal death event and may be the first trigger of the memory impairment [ 21 ].”
BackgroundAssociative memory deficits in mild cognitive impairment: The role of hippocampal formation
Atienza, M., da Silva, K. C. A., González‐Escamilla, G., Gil-Neciga, E., Gonzalez, A. S., & Cantero, J. L. (2011) · NeuroImage · doi:10.1016/j.neuroimage.2011.05.047 · Cited by 57
“The hippocampal CA1 is not only one of the first regions to be affected by AD neuropathology (Van Hoesen and Hyman, 1990) but its progressive deterioration has also been reported to correlate with the stage and the duration of the illness (Bobinski et al., 1995, 1997).”
Trujillo‐Estrada, L., Dávila, J. C., Sánchez‐Mejías, E., Sanchez-Varo, R. M., Gómez-Arboledas, Á., Vizuete, M., Vitórica, J., & Gutiérrez, A. (2014) · Journal of Alzheimer s Disease · doi:10.3233/jad-140495 · Cited by 58
Daulatzai, M. A. (2013) · Neurotoxicity Research · doi:10.1007/s12640-013-9407-2 · Cited by 56
“The more severely affected AD patients (e.g., those that were mute and immobile) had significantly lower neuronal counts in the CA1, CA2, CA4 (and the subiculum) (Bobinski et al. 1995, 1997).”
BackgroundSex-specific risk of cardiovascular disease and cognitive decline: pregnancy and menopause
Miller, V. M., Garovic, V. D., Kantarci, K., Barnes, J. N., Jayachandran, M., Mielke, M. M., Joyner, M. J., Shuster, L. T., & Rocca, W. A. (2013) · Biology of Sex Differences · doi:10.1186/2042-6410-4-6 · Cited by 57
“A direct relationship has been identified between hippocampal volumes on MRI and hippocampal neuronal density at autopsy in cognitively normal older adults and patients with Alzheimer’s disease [190].”
BackgroundApostolova, L. G., Hwang, K., Omid Kohannim, A., Avila, D., Elashoff, D. A., Jack, C. R., Shaw, L. M. J., Trojanowski, J. Q., Weiner, M. W., & Thompson, P. M. (2014) · NeuroImage Clinical · doi:10.1016/j.nicl.2013.12.012 · Cited by 59
“…Toledo-Morrell et al., 2000; Fleischman et al., 2005; Mortimer et al., 2004) and with AD pathologic markers such as neuronal and neurofibrillary tangle counts and Braak and Braak pathological stages (Apostolova et al., 2010b; Bobinski et al., 1995, 1997; Schonheit et al., 2004; Zarow et al., 2005).”
Hall, G. F., Lee, V. M. ‐., Lee, G. S., & Yao, J. (2001) · American Journal Of Pathology · doi:10.1016/s0002-9440(10)63962-4 · Cited by 54
Lee, P., Ryoo, H., Park, J., Jeong, Y., & Initiative, A. D. N. (2017) · Journal of Clinical Neurology · doi:10.3988/jcn.2017.13.2.144 · Cited by 52
Metadata
- Authors
- BOBINSKI, M., WEGIEL, J., TARNAWSKI, M., BOBINSKI, M., REISBERG, B., DE LEON, M. J., MILLER, D. C., & WISNIEWSKI, H. M.
- Affiliations
- NYU Langone Health (US)
- Venue
- Journal of Neuropathology and Experimental Neurology
- Publisher
- Oxford University Press (OUP)
- Published
- 1997-04
- Volume
- 56
- Issue
- 4
- Pages
- 414-420
- ISSN
- 0022-3069 (ISSN-L)
- OpenAlex
- W2004027050
- Cited by
- 208
- References
- 0
- Citations by year
- 2026: 3 · 2025: 3 · 2024: 4 · 2023: 6 · 2022: 3 · 2021: 10 · 2020: 5 · 2019: 7 · 2018: 6 · 2017: 4 · 2016: 8 · 2015: 3 · 2014: 10 · 2013: 9 · 2012: 8
- FWCI
- 5.10
- Type
- journal article
- Language
- en
- Open access
- closed
- Locations
- Journal of Neuropathology & Experimental Neurology (publishedVersion)
- PubMed (publishedVersion)
- Funders
- National Institutes of Health (5p01ag004220-12)
- National Institute on Aging (AG04220, AG03051, R01AG003051, P30AG008051, AG 08051)
- Topics
- Life Sciences › Neuroscience › Cellular and Molecular Neuroscience › Alzheimer's disease research and treatments
- Health Sciences › Medicine › Psychiatry and Mental health › Dementia and Cognitive Impairment Research
- Life Sciences › Neuroscience › Neurology › Neuroinflammation and Neurodegeneration Mechanisms
- Keywords
- Alzheimer's disease, neuronal loss, neurofibrillary tangles, hippocampal formation, hippocampal subfields, CA1, CA4, subiculum, cornu ammonis, dentate gyrus, disease duration, disease severity, clinical staging
- MeSH terms
- Aged, Aged, 80 and over, Alzheimer Disease, Female, Hippocampus, Humans, Male, Neurofibrils, Neurons, Severity of Illness Index, Time Factors, Cell Death
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