Figure 4. Abnormal brain function and enhanced neuropathology and memory decline in cognitively normal APOE ε4 carriers.

(a) ¹⁸F-fluorodeoxyglucose PET images show that cognitively normal APOE ε4 carriers have lower glucose metabolism than do noncarriers. (b) APOE ε4 carriers exhibit a greater increase in functional MRI signal in brain regions associated with task performance, and show increases in additional regions compared with APOE ε3 carriers. (c) Age-related memory decline occurs more rapidly in APOE ε4 carriers than noncarriers, starting from age 55–60 years. (d) APOE ε4 carriers show increased cerebral Aβ deposition which persists in greater frequencies with age compared with noncarriers. Increased PiB binding and reduced CSF Aβ₄₂ levels reflect cerebral amyloid deposition. Abbreviations: Aβ, amyloid-β; APOE, apolipoprotein E; CSF, cerebrospinal fluid; PiB, Pittsburg compund B. Part a, is modified, with permission from the National Academy of Science, USA © Small, G. W. et al. Proc. Natl Acad. Sci. USA 97, 6037–6042 (2000). Part b, is modified, with permission from the Massachusetts Medical Society © Bookheimer, S. Y. et al. N. Engl. J. Med. 343, 450–456 (2000). Part c, is modified, with permission from the Massachusetts Medical Society © Caselli et al. N. Engl. J. Med. 361, 255–263 (2009). Part d is modified, with permission, from John Wiley and Sons © Morris, J. C. et al. Ann. Neurol. 67, 122–131 (2010).