Research Paper Volume 16, Issue 10 pp 9072—9105

Figure 4. Heat map of correlation matrices of the proteins of CMA. (A, B) The correlation coefficient matrix among the proteins of CMA. (C) The difference matrix. Figure 4C shows that the degree of correlation between LAMP2 and the other three genes become stronger significantly as AD progresses. And the other three genes keep strong correlations among them. The inhibitory protein HSP90 unfolds substrates ready to be delivered to the LAMP2A complex for degradation, so the correlation between them becomes stronger. After unfolding, LAMP2A works with GFAP to deliver substrates to lysosome together, so the correlation becomes stronger. After finishing the delivery, the protein encoded by EEF1A1 dissociates GFAP to restore the LAMP2A complex in CMA, so the correlation becomes stronger. Thus, CMA becomes active with AD progression. The more detailed explanation of the molecular mechanism is described in Conclusion and Figure 6.