Imaging and cerebrospinal fluid biomarkers in the search for Alzheimer's disease mechanisms.
| Publication Type | Academic Article |
| Authors | Osorio R, Pirraglia E, Gumb T, Mantua J, Ayappa I, Williams S, Mosconi L, Glodzik L, de Leon M |
| Journal | Neurodegener Dis |
| Volume | 13 |
| Issue | 2-3 |
| Pagination | 163-5 |
| Date Published | 10/02/2013 |
| ISSN | 1660-2862 |
| Keywords | Alzheimer Disease, Biomarkers |
| Abstract | BACKGROUND: The pathophysiological process of Alzheimer's disease (AD) begins many years before the emergence of clinical symptoms (preclinical AD). A hypothetical biomarker progression in the pathogenesis of AD has been suggested, beginning with the deposition of amyloid-β (Aβ) and followed by increases in neurofibrillary tangles, synaptic loss, hippocampal atrophy, and lastly, cognitive impairment. OBJECTIVE: We explored the effect of several risk factors for AD on the pattern of AD biomarker expression in normal subjects. METHODS: AD biomarker evidence was examined at baseline in 96 cognitively normal elderly subjects with none or at least one of the following: ApoE4+ allele, a maternal history of AD (mFHx), sleep-disordered breathing (SDB), and longitudinal evidence of decline to mild cognitive impairment or AD (decliners) at follow-up. RESULTS: Decliners and ApoE4+ subjects presented with expected reduced cerebrospinal fluid Aβ42, elevated P-tau and T-tau. In addition, decliners had fluorodeoxyglucose positron emission tomography hypometabolism in the medial temporal lobe. Individuals with mFHx demonstrated no Aβ42 effect, but had elevations in P-tau and T-tau. SDB was found to be associated with elevated Aβ42, P-tau and T-tau, as well as with reduced medial temporal lobe glucose metabolic rates. CONCLUSION: Our results indicate a heterogeneous biomarker expression, suggesting diversity of AD pathways in at-risk presymptomatic subjects. |
| DOI | 10.1159/000355063 |
| PubMed ID | 24107601 |
| PubMed Central ID | PMC4022141 |