Domains of tau and apoE proteins, and apoE isoform distribution. Tau presents two domains that vary across isoforms: the projection domain (1N/2N) and the microtubule-binding region (MTBR), which can encompass either 3 or 4 repeats (3R/4R). These two domains are connected by the proline-rich region. ApoE presents three distinct regions: the N-terminal region (containing the receptor-binding domain), the C-terminal region (containing the lipid-binding domain), and a hinge region. The different apoE isoforms arise from amino acid substitutions at positions 112 and 158, where the APOE ε2 isoform (Cys112/Cys158) is the least frequent and the APOE ε3 isoform (Cys112/Arg158) is the most frequent. Within the AD population, the frequency of the risk gene, APOE ε4 (Arg112/Arg158), greatly increases.
Figure 1.

Domains of tau and apoE proteins, and apoE isoform distribution. Tau presents two domains that vary across isoforms: the projection domain (1N/2N) and the microtubule-binding region (MTBR), which can encompass either 3 or 4 repeats (3R/4R). These two domains are connected by the proline-rich region. ApoE presents three distinct regions: the N-terminal region (containing the receptor-binding domain), the C-terminal region (containing the lipid-binding domain), and a hinge region. The different apoE isoforms arise from amino acid substitutions at positions 112 and 158, where the APOE ε2 isoform (Cys112/Cys158) is the least frequent and the APOE ε3 isoform (Cys112/Arg158) is the most frequent. Within the AD population, the frequency of the risk gene, APOE ε4 (Arg112/Arg158), greatly increases.

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