Beta-Amyloid Deposition and the Aging Brain
A central issue in cognitive neuroscience of aging research is pinpointing precise neural mechanisms that determine cognitive outcome in late adulthood as well as identifying early markers of less successful cognitive aging. One promising biomarker is beta amyloid (Aβ) deposition. Several new radiotracers have been developed that bind to fibrillar Aβ providing sensitive estimates of amyloid deposition in various brain regions. Aβ imaging has been primarily used to study patients with Alzheimer’s Disease (AD) and individuals with Mild Cognitive Impairment (MCI); however, there is now building data on Aβ deposition in healthy controls that suggest at least 20% and perhaps as much as a third of healthy older adults show significant deposition. Considerable evidence suggests amyloid deposition precedes declines in cognition and may be the initiator in a cascade of events that indirectly leads to age-related cognitive decline. We review studies of Aβ deposition imaging in AD, MCI, and normal adults, its cognitive consequences, and the role of genetic risk and cognitive reserve.
KeywordsAging Beta-amyloid Brain Cognitive reserve fMRI PET
Preparation of this paper was supported by National Institutes of Health grant AG-006265-23 to Denise Park.
The authors have no financial disclosures to report.
- Bourgeat, P., Villemagne, V.L., Fripp, J., Pike, K.E., Raniga, P., Acosta, O., et al. (2009). Relation between amyloid burden, brain atrophy and memory in Alzheimer’s disease. Alzheimer’s Association 2009 International Conference on Alzheimer’s Disease (ICAD 2009), July.Google Scholar
- Braak, H., & Braak, E. (1996). Evolution of the neuropathology of Alzheimer’s disease. Acta Neurologica Scandinavica, 165, 3–12.Google Scholar
- Braskie, M.N., Klunder, A.D., Hayashi, K.M., Protas, H., Kepe, V., Miller, K. J., et al. (2008). Plaque and tangle imaging and cognition in normal aging and Alzheimer’s disease. Neurobiology of Aging. doi: 10.1016/j.neurobiolaging.2008.09.012.
- Buckner, R. L., Snyder, A. Z., Shannon, B. J., LaRossa, G., Sachs, R., Fotenos, A. F., et al. (2005). Molecular, structural, and functional characterization of Alzheimer’s disease: evidence for a relationship between default activity, amyloid, and memory. Journal of Neuroscience, 25, 7709–7717.CrossRefPubMedGoogle Scholar
- Dickerson, B. C., Bakkour, A., Salat, D. H., Feczko, E., Pacheco, J., Greve, D. N., et al. (2009). The cortical signature of Alzheimer’s disease: regionally specific cortical thinning relates to symptom severity in very mild to mild AD dementia and is detectable in asymptomatic amyloid-positive individuals. Cerebral Cortex, 19, 497–510.CrossRefPubMedGoogle Scholar
- Diniz, B. S., Pinto, J. A., & Forlenza, O. V. (2008). Do CSF total tau, phosphorylated tau, and beta-amyloid 42 help to predict progression of mild cognitive impairment to Alzheimer’s disease? A systematic review and meta-analysis of the literature. World Journal of Biological Psychiatry, 9, 172–182.CrossRefPubMedGoogle Scholar
- Farrer, L. A., Cupples, L. A., Haines, J. L., Hyman, B., Kukull, W. A., Mayeux, R., et al. (1997). Effects of age, sex, and ethnicity on the association between apolipoprotein E genotype and Alzheimer disease. A meta-analysis. APOE and Alzheimer Disease meta analysis consortium. Journal of the American Medical Association, 278, 1349–1356.CrossRefPubMedGoogle Scholar
- Gutchess, A. H., Welsh, R. C., Hedden, T., Bangert, A., Minear, M., Liu, L. L., et al. (2005). Aging and the neural correlates of successful picture encoding: frontal activations compensate for decreased medial-temporal activity. Journal of Cognitive Neuroscience, 17, 84–96.CrossRefPubMedGoogle Scholar
- Ichise, M., Plett, S., Joshi, A., Stern, Y., van Heertum, R., Lowe, V., et al. (2008). Quantitative comparison of three novel 18F-labeled ligands for PET imaging of brain amyloid-β plaques in Alzheimer’s disease. Journal of Nuclear Medicine, 49, 214.Google Scholar
- Jack, C. R., Jr., Lowe, V. J., Weigand, S. D., Wiste, H. J., Senjem, M. L., Knopman, D. S., et al. (2009). Serial PIB and MRI in normal, mild cognitive impairment and Alzheimer’s disease: implications for sequence of pathological events in Alzheimer’s disease. Brain, 132, 1355–1365.CrossRefPubMedGoogle Scholar
- Kemppainen, N. M., Aalto, S., Karrasch, M., Någren, K., Savisto, N., Oikonen, V., et al. (2008). Cognitive reserve hypothesis: Pittsburgh Compound B and fluorodeoxyglucose positron emission tomography in relation to education in mild Alzheimer’s disease. Annals of Neurology, 63, 112–118.CrossRefPubMedGoogle Scholar
- Li, Y., Rinne, J. O., Mosconi, L., Pirraglia, E., Rusinek, H., DeSanti, S., et al. (2008). Regional analysis of FDG and PIB-PET images in normal aging, mild cognitive impairment, and Alzheimer’s disease. European Journal of Nuclear Medicine and Molecular Imaging, 35, 2169–2181.CrossRefPubMedGoogle Scholar
- Park, D. C., & Goh, J. O. (2009). Successful aging. In J. Cacioppo & G. Berntson (Eds.), Handbook of Cognitive Neuroscience for the Behavioral Sciences, Ch. 61 (pp. 1203–1219). Hoboken: Wiley.Google Scholar
- Raz, N., & Kennedy, K. M. (2009). A systems approach to age-related change: Neuroanatomical changes, their modifiers, and cognitive correlates. In W. Jagust & M. D’Esposito (Eds.), Imaging the aging brain, Ch 4 (pp. 43–70). Oxford UP: NYC.Google Scholar
- Scheinin, N.M., Aalto, S., Koikkalainen, J., Lötjönen, J., Karrasch, M., Kemppainen, N., et al. (2009). Follow-up of [11C]PIB uptake and brain volume in patients with Alzheimer disease and controls. Neurology, 73, 1186–1192.Google Scholar
- Schmidt, M. L., Lee, V. M., & Trojanowski, J. Q. (1990). Relative abundance of tau and neurofilament epitopes in hippocampal neurofibrillary tangles. American Journal of Pathology, 136, 1069–1075.Google Scholar
- Skovronsky, D., Coleman, R. E., Frey, K., Garg, P., Ichise, M., Lowe, V., et al. (2008). Results of multi-center clinical trials comparing four 18F PET amyloid-imaging agents: preclinical to clinical correlations. Journal of Nuclear Medicine Meeting Abstracts, 49(1), 34P.Google Scholar
- Small, G. W., Siddarth, P., Burggren, A. C., Kepe, V., Ercoli, L. M., Miller, K. J., et al. (2009). Influence of cognitive status, age, and APOE-4 genetic risk on brain FDDNP positron-emission tomography imaging in persons without dementia. Archives of General Psychiatry, 66, 81–87.CrossRefPubMedGoogle Scholar
- Thal, D.R., Capetillo-Zarate, E., Del Tredici, K., & Braak, H. (2006). The development of amyloid beta protein deposits in the aged brain. Science of Aging Knowledge Environment: SAGE KE, 2006(6), re1.Google Scholar
- Tolboom, N., Yaqub, M., Boellaard, R., Luurtsema, G., Windhorst, A.D., Scheltens, P., et al. (2009b). Test-retest variability of quantitative [(11)C]PIB studies in Alzheimer’s disease. European Journal of Nuclear Medicine and Molecular Imaging, 36, 1629–1638.Google Scholar
- Wong, D., Rosenberg, P., Zhou, Y., Kumar, A., Ravert, H., Brasic, J., et al. (2008). In vivo imaging of amyloid deposition in Alzheimer’s disease using the novel radioligand [18F] AV-45. Journal of Nuclear Medicine Meeting Abstracts, 49(1), 214P.Google Scholar