Related Content
Search Google Scholar for:
More Information
Related Jobs from ScienceCareers
|
|
Science 17 October 1997: Vol. 278. no. 5337, pp. 412 - 419 DOI: 10.1126/science.278.5337.412
|
|
Articles
Life and Death of Neurons in the Aging Brain
John H. Morrison,
*
Patrick R. Hof
Neurodegenerative disorders are characterized by extensive neuron
death that leads to functional decline, but the neurobiological correlates of functional decline in normal aging are less well defined.
For decades, it has been a commonly held notion that widespread neuron
death in the neocortex and hippocampus is an inevitable concomitant of
brain aging, but recent quantitative studies suggest that neuron death
is restricted in normal aging and unlikely to account for age-related
impairment of neocortical and hippocampal functions. In this article,
the qualitative and quantitative differences between aging and
Alzheimer's disease with respect to neuron loss are discussed, and
age-related changes in functional and biochemical attributes of
hippocampal circuits that might mediate functional decline in the
absence of neuron death are explored. When these data are viewed
comprehensively, it appears that the primary neurobiological substrates
for functional impairment in aging differ in important ways from those
in neurodegenerative disorders such as Alzheimer's disease.
J. H. Morrison is with the Neurobiology of Aging
Laboratories, the Fishberg Research Center for Neurobiology, and the
Department of Geriatrics and Adult Development, Mount Sinai School of
Medicine, New York, NY 10029, USA. P. R. Hof is with the
Neurobiology of Aging Laboratories, the Fishberg Research Center for
Neurobiology, the Department of Geriatrics and Adult Development, and
the Department of Ophthalmology, Mount Sinai School of Medicine, New
York, NY 10029, USA.
*
To whom correspondence should be addressed. E-mail:
morrison{at}cortex.neuro.mssm.edu
Read the Full Text
THIS ARTICLE HAS BEEN CITED BY OTHER ARTICLES:
- Neural Stem Cells Improve Memory in an Inducible Mouse Model of Neuronal Loss.
- T. R. Yamasaki, M. Blurton-Jones, D. A. Morrissette, M. Kitazawa, S. Oddo, and F. M. LaFerla (2007)
J. Neurosci.
27, 11925-11933
| Abstract »
| Full Text »
| PDF »
- Dendritic BC200 RNA in aging and in Alzheimer's disease.
- E. Mus, P. R. Hof, and H. Tiedge (2007)
PNAS
104, 10679-10684
| Abstract »
| Full Text »
| PDF »
- Novel Perspectives for Progesterone in Hormone Replacement Therapy, with Special Reference to the Nervous System.
- M. Schumacher, R. Guennoun, A. Ghoumari, C. Massaad, F. Robert, M. El-Etr, Y. Akwa, K. Rajkowski, and E.-E. Baulieu (2007)
Endocr. Rev.
28, 387-439
| Abstract »
| Full Text »
| PDF »
- Oxidative Stress, Mitochondrial DNA Mutation, and Apoptosis in Aging.
- H.-C. Lee and Y.-H. Wei (2007)
Experimental Biology and Medicine
232, 592-606
| Abstract »
| Full Text »
| PDF »
- {beta}-Site Amyloid Precursor Protein Cleaving Enzyme 1 Levels Become Elevated in Neurons around Amyloid Plaques: Implications for Alzheimer's Disease Pathogenesis.
- J. Zhao, Y. Fu, M. Yasvoina, P. Shao, B. Hitt, T. O'Connor, S. Logan, E. Maus, M. Citron, R. Berry, et al. (2007)
J. Neurosci.
27, 3639-3649
| Abstract »
| Full Text »
| PDF »
- Auditory cortical activity in amnestic mild cognitive impairment: relationship to subtype and conversion to dementia.
- E. J. Golob, R. Irimajiri, and A. Starr (2007)
Brain
130, 740-752
| Abstract »
| Full Text »
| PDF »
- Top-Down Modulation and Normal Aging.
- A. GAZZALEY and M. D'ESPOSITO (2007)
Ann. N.Y. Acad. Sci.
1097, 67-83
| Abstract »
| Full Text »
| PDF »
- Brain Aging and Its Modifiers: Insights from in Vivo Neuromorphometry and Susceptibility Weighted Imaging.
- N. RAZ, K. M RODRIGUE, and E. M. HAACKE (2007)
Ann. N.Y. Acad. Sci.
1097, 84-93
| Abstract »
| Full Text »
| PDF »
- LRRTM3 promotes processing of amyloid-precursor protein by BACE1 and is a positional candidate gene for late-onset Alzheimer's disease.
- J. Majercak, W. J. Ray, A. Espeseth, A. Simon, X.-P. Shi, C. Wolffe, K. Getty, S. Marine, E. Stec, M. Ferrer, et al. (2006)
PNAS
103, 17967-17972
| Abstract »
| Full Text »
| PDF »
- Therapeutic approaches to Alzheimer's disease.
- H.-W. Klafki, M. Staufenbiel, J. Kornhuber, and J. Wiltfang (2006)
Brain
129, 2840-2855
| Abstract »
| Full Text »
| PDF »
- Dendrites of rod bipolar cells sprout in normal aging retina.
- L. C. Liets, K. Eliasieh, D. A. van der List, and L. M. Chalupa (2006)
PNAS
103, 12156-12160
| Abstract »
| Full Text »
| PDF »
- Early-onset behavioral and synaptic deficits in a mouse model of Alzheimer's disease.
- J. S. Jacobsen, C.-C. Wu, J. M. Redwine, T. A. Comery, R. Arias, M. Bowlby, R. Martone, J. H. Morrison, M. N. Pangalos, P. H. Reinhart, et al. (2006)
PNAS
103, 5161-5166
| Abstract »
| Full Text »
| PDF »
- White matter damage on diffusion tensor imaging correlates with age-related cognitive decline.
- R. A. Charlton, T. R. Barrick, D. J. McIntyre, Y. Shen, M. O'Sullivan, F. A. Howe, C. A. Clark, R. G. Morris, and H. S. Markus (2006)
Neurology
66, 217-222
| Abstract »
| Full Text »
| PDF »
- Serotonin 1A receptors in the living brain of Alzheimer's disease patients.
- V. Kepe, J. R. Barrio, S.-C. Huang, L. Ercoli, P. Siddarth, K. Shoghi-Jadid, G. M. Cole, N. Satyamurthy, J. L. Cummings, G. W. Small, et al. (2006)
PNAS
103, 702-707
| Abstract »
| Full Text »
| PDF »
- Dissociation of neuropathology from severity of dementia in late-onset Alzheimer disease.
- I. Prohovnik, D. P. Perl, K. L. Davis, L. Libow, G. Lesser, and V. Haroutunian (2006)
Neurology
66, 49-55
| Abstract »
| Full Text »
| PDF »
- Neuroanatomy/pathology and the interplay of neurotransmitters in moderate to severe Alzheimer disease.
- P. T. Francis (2005)
Neurology
65, S5-S9
| Full Text »
- Frontal-Hippocampal Double Dissociation Between Normal Aging and Alzheimer's Disease.
- D. Head, A. Z. Snyder, L. E. Girton, J. C. Morris, and R. L. Buckner (2005)
Cereb Cortex
15, 732-739
| Abstract »
| Full Text »
| PDF »
- Differential Effects of Aging and Insulin-like Growth Factor-1 on Synapses in CA1 of Rat Hippocampus.
- L. Shi, M. C. Linville, E. W. Tucker, W. E. Sonntag, and J. K. Brunso-Bechtold (2005)
Cereb Cortex
15, 571-577
| Abstract »
| Full Text »
| PDF »
- Increasing Memory Load Modulates Regional Brain Activity in Older Adults as Measured by fMRI.
- J. R. Petrella, B. A. Townsend, A. P. Jha, L. A. Ziajko, M. J. Slavin, C. Lustig, S. J. Hart, and P. M. Doraiswamy (2005)
J Neuropsychiatry Clin Neurosci
17, 75-83
| Abstract »
| Full Text »
| PDF »
- Massive CA1/2 Neuronal Loss with Intraneuronal and N-Terminal Truncated A{beta}42 Accumulation in a Novel Alzheimer Transgenic Model.
- C. Casas, N. Sergeant, J.-M. Itier, V. Blanchard, O. Wirths, N. van der Kolk, V. Vingtdeux, E. van de Steeg, G. Ret, T. Canton, et al. (2004)
Am. J. Pathol.
165, 1289-1300
| Abstract »
| Full Text »
| PDF »
- Calpain Mediates Calcium-Induced Activation of the Erk1,2 MAPK Pathway and Cytoskeletal Phosphorylation in Neurons: Relevance to Alzheimer's Disease.
- Veeranna, T. Kaji, B. Boland, T. Odrljin, P. Mohan, B. S. Basavarajappa, C. Peterhoff, A. Cataldo, A. Rudnicki, N. Amin, et al. (2004)
Am. J. Pathol.
165, 795-805
| Abstract »
| Full Text »
| PDF »
- Absence of C1q Leads to Less Neuropathology in Transgenic Mouse Models of Alzheimer's Disease.
- M. I. Fonseca, J. Zhou, M. Botto, and A. J. Tenner (2004)
J. Neurosci.
24, 6457-6465
| Abstract »
| Full Text »
| PDF »
- Thinning of the Cerebral Cortex in Aging.
- D. H. Salat, R. L. Buckner, A. Z. Snyder, D. N. Greve, R. S.R. Desikan, E. Busa, J. C. Morris, A. M. Dale, and B. Fischl (2004)
Cereb Cortex
14, 721-730
| Abstract »
| Full Text »
| PDF »
- Effects of Age and Caloric Restriction on Brain Neuronal Cell Death/Survival.
- A. HIONA and C. LEEUWENBURGH (2004)
Ann. N.Y. Acad. Sci.
1019, 96-105
| Abstract »
| Full Text »
| PDF »
- From the Cover: Dynamic mapping of human cortical development during childhood through early adulthood.
- N. Gogtay, J. N. Giedd, L. Lusk, K. M. Hayashi, D. Greenstein, A. C. Vaituzis, T. F. Nugent III, D. H. Herman, L. S. Clasen, A. W. Toga, et al. (2004)
PNAS
101, 8174-8179
| Abstract »
| Full Text »
| PDF »
- Selective vulnerability of dentate granule cells prior to amyloid deposition in PDAPP mice: Digital morphometric analyses.
- C.-C. Wu, F. Chawla, D. Games, R. E. Rydel, S. Freedman, D. Schenk, W. G. Young, J. H. Morrison, and F. E. Bloom (2004)
PNAS
101, 7141-7146
| Abstract »
| Full Text »
| PDF »
- Sister grouping of chimpanzees and humans as revealed by genome-wide phylogenetic analysis of brain gene expression profiles.
- M. Uddin, D. E. Wildman, G. Liu, W. Xu, R. M. Johnson, P. R. Hof, G. Kapatos, L. I. Grossman, and M. Goodman (2004)
PNAS
101, 2957-2962
| Abstract »
| Full Text »
| PDF »
- Normal Genetic Variation, Cognition, and Aging.
- P. M. Greenwood and R. Parasuraman (2003)
Behav Cogn Neurosci Rev
2, 278-306
| Abstract »
| PDF »
- Age-related Dendritic and Spine Changes in Corticocortically Projecting Neurons in Macaque Monkeys.
- H. Duan, S. L. Wearne, A. B. Rocher, A. Macedo, J. H. Morrison, and P. R. Hof (2003)
Cereb Cortex
13, 950-961
| Abstract »
| Full Text »
| PDF »
- Priorities in Perioperative Geriatrics.
- D. J. Cook and G. A. Rooke (2003)
Anesth. Analg.
96, 1823-1836
| Full Text »
| PDF »
- Tangle and neuron numbers, but not amyloid load, predict cognitive status in Alzheimer's disease.
- P. Giannakopoulos, F. R. Herrmann, T. Bussiere, C. Bouras, E. Kovari, D. P. Perl, J. H. Morrison, G. Gold, and P. R. Hof (2003)
Neurology
60, 1495-1500
| Abstract »
| Full Text »
| PDF »
- Amyloid deposition in the hippocampus and entorhinal cortex: Quantitative analysis of a transgenic mouse model.
- J. F. Reilly, D. Games, R. E. Rydel, S. Freedman, D. Schenk, W. G. Young, J. H. Morrison, and F. E. Bloom (2003)
PNAS
100, 4837-4842
| Abstract »
| Full Text »
| PDF »
- Longitudinal Magnetic Resonance Imaging Studies of Older Adults: A Shrinking Brain.
- S. M. Resnick, D. L. Pham, M. A. Kraut, A. B. Zonderman, and C. Davatzikos (2003)
J. Neurosci.
23, 3295-3301
| Abstract »
| Full Text »
| PDF »
- Dentate gyrus volume is reduced before onset of plaque formation in PDAPP mice: A magnetic resonance microscopy and stereologic analysis.
- J. M. Redwine, B. Kosofsky, R. E. Jacobs, D. Games, J. F. Reilly, J. H. Morrison, W. G. Young, and F. E. Bloom (2003)
PNAS
100, 1381-1386
| Abstract »
| Full Text »
| PDF »
- Dynamics of Gray Matter Loss in Alzheimer's Disease.
- P. M. Thompson, K. M. Hayashi, G. de Zubicaray, A. L. Janke, S. E. Rose, J. Semple, D. Herman, M. S. Hong, S. S. Dittmer, D. M. Doddrell, et al. (2003)
J. Neurosci.
23, 994-1005
| Abstract »
| Full Text »
| PDF »
- The Contribution of Functional Brain Imaging to Our Understanding of Cognitive Aging.
- A. Gazzaley and M. D'Esposito (2003)
Sci. Aging Knowl. Environ.
2003, pe2-2
| Abstract »
| Full Text »
- fMRI studies of associative encoding in young and elderly controls and mild Alzheimer's disease.
- R A Sperling, J F Bates, E F Chua, A J Cocchiarella, D M Rentz, B R Rosen, D L Schacter, and M S Albert (2003)
J. Neurol. Neurosurg. Psychiatry
74, 44-50
| Abstract »
| Full Text »
| PDF »
- Neuron Number in the Parahippocampal Region is Preserved in Aged Rats with Spatial Learning Deficits.
- P. R. Rapp, P. S. Deroche, Y. Mao, and R. D. Burwell (2002)
Cereb Cortex
12, 1171-1179
| Abstract »
| Full Text »
| PDF »
- Oxidative Stress, Mitochondrial DNA Mutation, and Impairment of Antioxidant Enzymes in Aging.
- Y.-H. Wei and H.-C. Lee (2002)
Experimental Biology and Medicine
227, 671-682
| Abstract »
| Full Text »
| PDF »
- Herpes simplex virus type 1 infection prevents detachment of nerve growth factor-differentiated PC12 cells in culture.
- M. J. Moxley, T. M. Block, H.-C. Liu, N. W. Fraser, G.-C. Perng, S. L. Wechsler, and Y.-H. Su (2002)
J. Gen. Virol.
83, 1591-1600
| Abstract »
| Full Text »
| PDF »
- Cyclin-Dependent Kinase 5 Is Required for Associative Learning.
- A. Fischer, F. Sananbenesi, C. Schrick, J. Spiess, and J. Radulovic (2002)
J. Neurosci.
22, 3700-3707
| Abstract »
| Full Text »
| PDF »
- The Role of Apoptosis in the Normal Aging Brain, Skeletal Muscle, and Heart.
- M. POLLACK, S. PHANEUF, A. DIRKS, and C. LEEUWENBURGH (2002)
Ann. N.Y. Acad. Sci.
959, 93-107
| Abstract »
| Full Text »
| PDF »
- Amyloid-Associated Neuron Loss and Gliogenesis in the Neocortex of Amyloid Precursor Protein Transgenic Mice.
- L. Bondolfi, M. Calhoun, F. Ermini, H. G. Kuhn, K.-H. Wiederhold, L. Walker, M. Staufenbiel, and M. Jucker (2002)
J. Neurosci.
22, 515-522
| Abstract »
| Full Text »
| PDF »
- The Effects of Age on the Cells in Layer 1 of Primate Cerebral Cortex.
- A. Peters and C. Sethares (2002)
Cereb Cortex
12, 27-36
| Abstract »
| Full Text »
| PDF »
- Cells in human postmortem brain tissue slices remain alive for several weeks in culture.
- R. W. H. VERWER, W. T. J. M. C. HERMENS, P. A. DIJKHUIZEN, O. TER BRAKE, R. E. BAKER, A. SALEHI, A. A. SLUITER, M. J. M. KOK, L. J. MULLER, J. VERHAAGEN, et al. (2002)
FASEB J
16, 54-60
| Abstract »
| Full Text »
| PDF »
- Apoptosis and Aging: Role of the Mitochondria.
- M. Pollack and C. Leeuwenburgh (2001)
J. Gerontol. A Biol. Sci. Med. Sci.
56, B475-482
| Abstract »
| Full Text »
| PDF »
- Evidence for cortical ""disconnection"" as a mechanism of age-related cognitive decline.
- M. O'Sullivan, D. K. Jones, P. E. Summers, R. G. Morris, S. C. R. Williams, and H. S. Markus (2001)
Neurology
57, 632-638
| Abstract »
| Full Text »
| PDF »
- Neuronal Hypertrophy in the Neocortex of Patients with Temporal Lobe Epilepsy.
- S. Bothwell, G. E. Meredith, J. Phillips, H. Staunton, C. Doherty, E. Grigorenko, S. Glazier, S. A. Deadwyler, C. A. O'Donovan, and M. Farrell (2001)
J. Neurosci.
21, 4789-4800
| Abstract »
| Full Text »
| PDF »
- Gender differences in predictors of mortality in nursing home residents with AD.
- K.L. Lapane, G. Gambassi, F. Landi, A. Sgadari, V. Mor, and R. Bernabei (2001)
Neurology
56, 650-654
| Abstract »
| Full Text »
| PDF »
- Nontropic actions of neurotrophins: Subcortical nerve growth factor gene delivery reverses age-related degeneration of primate cortical cholinergic innervation.
- J. M. Conner, M. A. Darracq, J. Roberts, and M. H. Tuszynski (2001)
PNAS
98, 1941-1946
| Abstract »
| Full Text »
| PDF »
- Sarcopenia: Current Concepts.
- R. Roubenoff and V. A. Hughes (2000)
J. Gerontol. A Biol. Sci. Med. Sci.
55, 716M-724
| Abstract »
| Full Text »
- Corticolimbic Interactions Associated with Performance on a Short-Term Memory Task Are Modified by Age.
- V. Della-Maggiore, A. B. Sekuler, C. L. Grady, P. J. Bennett, R. Sekuler, and A. R. McIntosh (2000)
J. Neurosci.
20, 8410-8416
| Abstract »
| Full Text »
| PDF »
- Homocysteine Elicits a DNA Damage Response in Neurons That Promotes Apoptosis and Hypersensitivity to Excitotoxicity.
- I. I. Kruman, C. Culmsee, S. L. Chan, Y. Kruman, Z. Guo, L. Penix, and M. P. Mattson (2000)
J. Neurosci.
20, 6920-6926
| Abstract »
| Full Text »
| PDF »
- Circuit-Specific Alterations in Hippocampal Synaptophysin Immunoreactivity Predict Spatial Learning Impairment in Aged Rats.
- T. D. Smith, M. M. Adams, M. Gallagher, J. H. Morrison, and P. R. Rapp (2000)
J. Neurosci.
20, 6587-6593
| Abstract »
| Full Text »
| PDF »
- One-year Age Changes in MRI Brain Volumes in Older Adults.
- S. M. Resnick, A. F. Goldszal, C. Davatzikos, S. Golski, M. A. Kraut, E. J. Metter, R. N. Bryan, and A. B. Zonderman (2000)
Cereb Cortex
10, 464-472
| Abstract »
| Full Text »
| PDF »
- Corpus Callosum Measurement as an in Vivo Indicator for Neocortical Neuronal Integrity, but not White Matter Pathology, in Alzheimer's Disease.
- H. HAMPEL, S. J. TEIPEL, G. E. ALEXANDER, B. HORWITZ, P. PIETRINI, H. HIPPIUS, H.-J. MOLLER, M. B. SCHAPIRO, and S. I. RAPOPORT (2000)
Ann. N.Y. Acad. Sci.
903, 470-476
| Full Text »
| PDF »
- Compensatory sleep response to 12 h wakefulness in young and old rats.
- P. J. Shiromani, J. Lu, D. Wagner, J. Thakkar, M. A. Greco, R. Basheer, and M. Thakkar (2000)
Am J Physiol Regulatory Integrative Comp Physiol
278, R125-R133
| Abstract »
| Full Text »
| PDF »
- Age-associated neuronal atrophy occurs in the primate brain and is reversible by growth factor gene therapy.
- D. E. Smith, J. Roberts, F. H. Gage, and M. H. Tuszynski (1999)
PNAS
96, 10893-10898
| Abstract »
| Full Text »
| PDF »
- Caspase-6 Role in Apoptosis of Human Neurons, Amyloidogenesis, and Alzheimer's Disease.
- A. LeBlanc, H. Liu, C. Goodyer, C. Bergeron, and J. Hammond (1999)
J. Biol. Chem.
274, 23426-23436
| Abstract »
| Full Text »
| PDF »
- Predictors of mortality in patients with Alzheimer's disease living in nursing homes.
- G. Gambassi, F. Landi, K. L Lapane, A. Sgadari, V. Mor, and R. Bernabei (1999)
J. Neurol. Neurosurg. Psychiatry
67, 59-65
| Abstract »
| Full Text »
- A neuronal morphologic type unique to humans and great apes.
- E. A. Nimchinsky, E. Gilissen, J. M. Allman, D. P. Perl, J. M. Erwin, and P. R. Hof (1999)
PNAS
96, 5268-5273
| Abstract »
| Full Text »
| PDF »
- The biochemical pathway of neurofibrillary degeneration in aging and Alzheimer's disease.
- A. Delacourte, J. P. David, N. Sergeant, L. Buee, A. Wattez, P. Vermersch, F. Ghozali, C. Fallet-Bianco, F. Pasquier, F. Lebert, et al. (1999)
Neurology
52, 1158
| Abstract »
| Full Text »
- Prefrontal Gray and White Matter Volumes in Healthy Aging and Alzheimer Disease.
- D. H. Salat, J. A. Kaye, and J. S. Janowsky (1999)
Arch Neurol
56, 338-344
| Abstract »
| Full Text »
| PDF »
- Role of ERAB/L-3-Hydroxyacyl-coenzyme A Dehydrogenase Type II Activity in Abeta -induced Cytotoxicity.
- S. Du Yan, Y. Shi, A. Zhu, J. Fu, H. Zhu, Y. Zhu, L. Gibson, E. Stern, K. Collison, F. Al-Mohanna, et al. (1999)
J. Biol. Chem.
274, 2145-2156
| Abstract »
| Full Text »
| PDF »
- Plasticity of hippocampal corticosteroid receptors during aging in the rat.
- A. H. S. hassan, V. K. Patchev, P. V. Rosenstiel, F. Holsboer, and O. F. X. Almeida (1999)
FASEB J
13, 115-122
| Abstract »
| Full Text »
- Genetic Neurodegenerative Diseases: The Human Illness and Transgenic Models.
- D. L. Price, S. S. Sisodia, and D. R. Borchelt (1998)
Science
282, 1079-1083
| Abstract »
| Full Text »
- Reduction of O-Linked N-Acetylglucosamine-Modified Assembly Protein-3 in Alzheimer's Disease.
- P. J. Yao and P. D. Coleman (1998)
J. Neurosci.
18, 2399-2411
| Abstract »
| Full Text »
| PDF »
- GABAA and alpha -Amino-3-hydroxy-5-methylsoxazole-4-propionate Receptors Are Differentially Affected by Aging in the Rat Hippocampus.
- D. Ruano, F. Araujo, E. Revilla, J. Vela, O. Bergis, and J. Vitorica (2000)
J. Biol. Chem.
275, 19585-19593
| Abstract »
| Full Text »
| PDF »
- Pro-caspase-8 Is Predominantly Localized in Mitochondria and Released into Cytoplasm upon Apoptotic Stimulation.
- Z.-H. Qin, Y. Wang, K. K. Kikly, E. Sapp, K. B. Kegel, N. Aronin, and M. DiFiglia (2001)
J. Biol. Chem.
276, 8079-8086
| Abstract »
| Full Text »
| PDF »
- Apoptosis in skeletal muscle with aging.
- A. Dirks and C. Leeuwenburgh (2002)
Am J Physiol Regulatory Integrative Comp Physiol
282, R519-R527
| Abstract »
| Full Text »
| PDF »
|
|