Fluctuations of CSF amyloid-β levels: Implications for a diagnostic and therapeutic biomarker
Abstract
OBJECTIVE: To investigate the stability and time course of human CSF amyloid-beta (Abeta) levels over hours. METHODS: Fifteen nondemented participants had CSF sampled hourly for up to 36 hours via indwelling lumbar catheter. CSF Abeta(1-x), Abeta(1-40), and Abeta(1-42) were measured by ELISA in each hourly CSF sample. RESULTS: Significant variation in Abeta levels of 1.5- to fourfold was detected over 36 hours of serially sampling in individual subjects. Abeta(40), Abeta(42), and Abeta(1-X) are highly correlated over time indicating that similar processes likely regulate the level of these species. On average, the fluctuations of Abeta levels appear to be time of day or activity dependent. CONCLUSION: Diagnostic and therapeutic trials that measure Abeta should control for the time of CSF sampling to minimize variability.
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APP and Aβ homeostasis are exquisitely regulated processes, and bioenergetic metabolism regulates these processes.
“Overall, we feel we can confidently state APP and Aβ homeostasis are exquisitely regulated processes, and bioenergetic metabolism regulates these processes.”
From The Alzheimer’s disease mitochondrial cascade hypothesis: progress and perspectives (2014) · cites this paper as [183]
Cites
The Amyloid Hypothesis of Alzheimer’s Disease: Progress and Problems on the Road to Therapeutics
Hardy, J., & Selkoe, D. J. (2002) · Science · doi:10.1126/science.1072994 · Cited by 13,864 · see citing works
Hansson, O., Zetterberg, H., Buchhave, P., Londos, E., Blennow, K., & Minthon, L. (2006) · The Lancet Neurology · doi:10.1016/s1474-4422(06)70355-6 · Cited by 1,700 · see citing works
APP Processing and Synaptic Function
Kamenetz, F., Tomita, T., Hsieh, H., Seabrook, G., Borchelt, D., Iwatsubo, T., Sisodia, S., & Malinow, R. (2003) · Neuron · doi:10.1016/s0896-6273(03)00124-7 · Cited by 1,644 · see citing works
Synaptic Activity Regulates Interstitial Fluid Amyloid-β Levels In Vivo
Cirrito, J. R., Yamada, K. A., Finn, M. B., Sloviter, R. S., Bales, K. R., May, P. C., Schoepp, D. D., Paul, S. M., Mennerick, S., & Holtzman, D. M. (2005) · Neuron · doi:10.1016/j.neuron.2005.10.028 · Cited by 1,265 · see citing works
Self-citationFagan, A. M., Mintun, M. A., Mach, R. H., Lee, S., Dence, C. S., Shah, A. R., LaRossa, G. N., Spinner, M. L., Klunk, W. E., Mathis, C. A., et al. (2006) · Annals of Neurology · doi:10.1002/ana.20730 · Cited by 1,246 · see citing works
Self-citationFagan, A. M., Roe, C. M., Xiong, C., Mintun, M. A., Morris, J. C., & Holtzman, D. M. (2007) · Archives of Neurology · doi:10.1001/archneur.64.3.noc60123 · Cited by 897 · see citing works
Self-citationAndreasen, N., Hesse, C., Davidsson, P., Minthon, L., Wallin, A., Winblad, B., Vanderstichele, H., Vanmechelen, E., & Blennow, K. (1999) · Archives of Neurology · doi:10.1001/archneur.56.6.673 · Cited by 660 · see citing works
Sunderland, T., Linker, G., Mirza, N., Putnam, K. T., Friedman, D. L., Kimmel, L. H., Bergeson, J., Manetti, G. J., Zimmermann, M., Tang, B., et al. (2003) · JAMA · doi:10.1001/jama.289.16.2094 · Cited by 656 · see citing works
Human amyloid-β synthesis and clearance rates as measured in cerebrospinal fluid in vivo
Bateman, R. J., Munsell, L. Y., Morris, J. C., Swarm, R., Yarasheski, K. E., & Holtzman, D. M. (2006) · Nature Medicine · doi:10.1038/nm1438 · Cited by 599 · see citing works
Self-citationCirrito, J. R., May, P. C., O'Dell, M. A., Taylor, J. W., Parsadanian, M., Cramer, J. W., Audia, J. E., Nissen, J. S., Bales, K. R., Paul, S. M., et al. (2003) · The Journal of Neuroscience · doi:10.1523/jneurosci.23-26-08844.2003 · Cited by 394 · see citing works
Self-citationKanai, M., Matsubara, E., Isoe, K., Urakami, K., Nakashima, K., Arai, H., Sasaki, H., Abe, K., Iwatsubo, T., Kosaka, T., et al. (1998) · Annals of Neurology · doi:10.1002/ana.410440108 · Cited by 340 · see citing works
Golde, T. E., Eckman, C. B., & Younkin, S. G. (2000) · Biochimica et Biophysica Acta (BBA) - Molecular Basis of Disease · doi:10.1016/s0925-4439(00)00043-0 · Cited by 300 · see citing works
Nostrand, W. E. V., Wagner, S. L., Shankle, W. R., Farrow, J. S., Dick, M. B., Rozemüller, A. J. M., Kuiper, M. A., Wolters, E. C., Zimmerman, J. B., & Cotman, C. W. (1992) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.89.7.2551 · Cited by 205 · see citing works
Cerebrospinal fluid sulfatide is decreased in subjects with incipient dementia
Han, X., Fagan, A. M., Cheng, H., Morris, J. C., Xiong, C., & Holtzman, D. M. (2003) · Annals of Neurology · doi:10.1002/ana.10618 · Cited by 111 · see citing works
Self-citationVanderstichele, H., Meyer, G. D., Andreasen, N., Kostanjevečki, V., Wallin, A., Olsson, A., Blennow, K., & Vanmechelen, E. (2005) · Clinical Chemistry · doi:10.1373/clinchem.2005.051201 · Cited by 80 · see citing works
(2006) · The Lancet Neurology · doi:10.1016/s1474-4422(06)70393-3 · Cited by 1 · see citing works
Flagged first, then by citations
Cited by
Sorted by citations
High-precision plasma β-amyloid 42/40 predicts current and future brain amyloidosis
Schindler, S. E., Bollinger, J. G., Ovod, V., Mawuenyega, K. G., Li, Y., Gordon, B. A., Holtzman, D. M., Morris, J. C., Benzinger, T. L. S., Xiong, C., et al. (2019) · Neurology · doi:10.1212/wnl.0000000000008081 · Cited by 885 · see citing works
Self-citationThe Alzheimer’s disease mitochondrial cascade hypothesis: progress and perspectives
Swerdlow, R. H., Burns, J. M., & Khan, S. M. (2014) · Biochimica et Biophysica Acta (BBA) - Molecular Basis of Disease · doi:10.1016/j.bbadis.2013.09.010 · Cited by 786 · see citing works
Visser, P. J., Verhey, F., Knol, D. L., Scheltens, P., Wahlund, L.-O., Freund-Levi, Y., Tsolaki, M., Minthon, L., Wallin, Å. K., Hampel, H., et al. (2009) · The Lancet Neurology · doi:10.1016/s1474-4422(09)70139-5 · Cited by 614 · see citing works
Roh, J. H., Huang, Y., Bero, A. W., Kasten, T., Stewart, F. R., Bateman, R. J., & Holtzman, D. M. (2012) · Science Translational Medicine · doi:10.1126/scitranslmed.3004291 · Cited by 563 · see citing works
Self-citationOoms, S., Overeem, S., Besse, K., Rikkert, M. O., Verbeek, M., & Claassen, J. A. H. R. (2014) · JAMA Neurology · doi:10.1001/jamaneurol.2014.1173 · Cited by 438 · see citing works
del Campo, M., Mollenhauer, B., Bertolotto, A., Engelborghs, S., Hampel, H., Simonsen, A. H., Kapaki, E., Kruse, N., Le Bastard, N., Lehmann, S., et al. (2012) · Biomarkers in Medicine · doi:10.2217/bmm.12.46 · Cited by 343 · see citing works
Vanderstichele, H., Bibl, M., Engelborghs, S., Le Bastard, N., Lewczuk, P., Molinuevo, J. L., Parnetti, L., Perret‐Liaudet, A., Shaw, L. M., Teunissen, C., et al. (2012) · Alzheimer's & Dementia · doi:10.1016/j.jalz.2011.07.004 · Cited by 358 · see citing works
A γ‐secretase inhibitor decreases amyloid‐β production in the central nervous system
Bateman, R. J., Siemers, E. R., Mawuenyega, K. G., Wen, G., Browning, K. R., Sigurdson, W. C., Yarasheski, K. E., Friedrich, S. W., DeMattos, R. B., May, P. C., et al. (2009) · Annals of Neurology · doi:10.1002/ana.21623 · Cited by 322 · see citing works
Self-citationKlyubin, I., Betts, V., Welzel, A. T., Blennow, K., Zetterberg, H., Wallin, A., Lemere, C. A., Cullen, W. K., Peng, Y., Wisniewski, T., et al. (2008) · The Journal of Neuroscience · doi:10.1523/jneurosci.5161-07.2008 · Cited by 321 · see citing works
Amyloid-β Dynamics Correlate with Neurological Status in the Injured Human Brain
Brody, D. L., Magnoni, S., Schwetye, K. E., Spinner, M. L., Esparza, T. J., Stocchetti, N., Zipfel, G. J., & Holtzman, D. M. (2008) · Science · doi:10.1126/science.1161591 · Cited by 295 · see citing works
Self-citationHigh‐molecular‐weight β‐amyloid oligomers are elevated in cerebrospinal fluid of Alzheimer patients
Fukumoto, H., Tokuda, T., Kasai, T., Ishigami, N., Hidaka, H., Kondo, M., Allsop, D., & Nakagawa, M. (2010) · The FASEB Journal · doi:10.1096/fj.09-150359 · Cited by 264 · see citing works
Biochemical markers in persons with preclinical familial Alzheimer disease
Ringman, J. M., Younkin, S. G., Pratico, D., Seltzer, W., Cole, G. M., Geschwind, D. H., Rodriguez-Agudelo, Y., Schaffer, B., Fein, J., Sokolow, S., et al. (2008) · Neurology · doi:10.1212/01.wnl.0000303973.71803.81 · Cited by 198 · see citing works
Branger, P., Arenaza-Urquijo, E. M., Tomadesso, C., Mézenge, F., André, C., de Flores, R., Mutlu, J., de La Sayette, V., Eustache, F., Chételat, G., et al. (2016) · Neurobiology of Aging · doi:10.1016/j.neurobiolaging.2016.02.009 · Cited by 186 · see citing works
Distinct Pools of β-Amyloid in Alzheimer Disease–Affected Brain: A Clinicopathologic Study
Steinerman, J. R., Irizarry, M., Scarmeas, N., Raju, S., Brandt, J., Albert, M., Blacker, D., Hyman, B., & Stern, Y. (2008) · Archives of Neurology · doi:10.1001/archneur.65.7.906 · Cited by 104 · see citing works
Lloret, M.-A., Cervera-Ferri, A., Nepomuceno, M., Monllor, P., Esteve, D., & Lloret, A. (2020) · International Journal of Molecular Sciences · doi:10.3390/ijms21031168 · Cited by 68 · see citing works
CSF amyloid 38 as a novel diagnostic marker for dementia with Lewy bodies
Mulugeta, E., Londos, E., Ballard, C., Alves, G., Zetterberg, H., Blennow, K., Skogseth, R., Minthon, L., & Aarsland, D. (2011) · Journal of Neurology, Neurosurgery & Psychiatry · doi:10.1136/jnnp.2009.199398 · Cited by 54 · see citing works
Linking cerebrovascular defense mechanisms in brain ageing and Alzheimer's disease
Kalaria, R. N. (2009) · Neurobiology of Aging · doi:10.1016/j.neurobiolaging.2007.10.020 · Cited by 48 · see citing works
Herukka, S.-K., Rummukainen, J., Ihalainen, J., von und zu Fraunberg, M., Koivisto, A. M., Nerg, O., Puli, L. K., Seppälä, T. T., Zetterberg, H., Pyykkö, O. T., et al. (2015) · Journal of Alzheimer's Disease · doi:10.3233/jad-142862 · Cited by 43 · see citing works
Gerstner, J. R., Lenz, O., Vanderheyden, W. M., Chan, M. T., Pfeiffenberger, C., & Pack, A. I. (2017) · Journal of Neuroscience Research · doi:10.1002/jnr.23778 · Cited by 40 · see citing works
- Authors
- Bateman, R. J., Wen, G., Morris, J. C., & Holtzman, D. M.
- Affiliations
- Washington University in St. Louis (US)
- Venue
- Neurology
- Published
- 2007-02-27
- Volume
- 68
- Issue
- 9
- Pages
- 666-669
- ISSN
- 0028-3878 (ISSN-L)
- 1526-632X
- OpenAlex
- W2129379145
- Cited by
- 260
- References
- 17
- Citations by year
- 2026: 4 · 2025: 9 · 2024: 13 · 2023: 9 · 2022: 8 · 2021: 5 · 2020: 10 · 2019: 10 · 2018: 8 · 2017: 16 · 2016: 16 · 2015: 17 · 2014: 15 · 2013: 12 · 2012: 15
- FWCI
- 15.34
- Type
- journal article
- Language
- en
- Open access
- closed
- Locations
- Neurology (publishedVersion)
- PubMed (publishedVersion)
- Funders
- Deutsches Krebsforschungszentrum
- National Institute on Aging (L30 AG024455, K08AG027091, P50AG005681, P01AG003991)
- National Center for Research Resources (MO1RR00036, M01RR000036)
- Topics
- Health Sciences › Medicine › Physiology › Alzheimer's disease research and treatments
- Health Sciences › Medicine › Psychiatry and Mental health › Dementia and Cognitive Impairment Research
- Life Sciences › Neuroscience › Cellular and Molecular Neuroscience › Cerebrospinal fluid and hydrocephalus
- Keywords
- cerebrospinal fluid, amyloid-beta, Aβ40, amyloid-beta 42, temporal variation, Alzheimer's disease biomarkers
- MeSH terms
- Adult, Aged, Alzheimer Disease, Female, Humans, Male, Middle Aged, Reference Values, Sensitivity and Specificity, Time Factors, Reproducibility of Results, Biomarkers, Amyloid beta-Peptides
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