Study 2: Congophilic staining is observed in mice throughout both ipsilateral hippocampus (A, B and C) and ipsilateral anterior cortex (D, E and F).

<p>Congophilic staining in the hippocampus of animals that received intracranial injections of rAAV- IDE-n (B) or IDE-s (C) is unchanged compared to staining in those animals that received injections of control vector rAAV- GFP (A). Congophilic staining in the anterior cortex of mice that received intracranial injections of rAAV- IDE-n (E) or NEP-s (F) is also unchanged compared to staining in mice that received control vector rAAV- GFP(D). Scale bar = 200 µm. Quantification of percent area of positive total congophilic staining is shown in G and H (hemisphere ipsilateral to injection sites). No significant differences were found. n = 8/group.</p

Study 3: CD68 (A-C) and CD45 (D-F) immunostaining is observed throughout the hippocampus of study mice.

<p>In the hippocampus, no significant differences are observed in the amount of total CD68 staining between the NEP-n, NEP-s, and NEP-m groups, but CD45 staining in NEP-s treated mice is greater than CD45 staining in NEP-m treated mice. Scale bar = 50 µm. Panels G and H present ANOVA analysis of the ratio of CD68 to congophilic staining, and of the ratio of quantitated CD45 to congophilic staining, respectively, in the hippocampus of study mice. The (*) indicates significance compared to NEP-m mice with p<0.05, and the (^∧) indicates significance compared to Tg control mice with p<0.05 or p<0.01 (°).Tg control (n = 9), NEP-n (n = 4), NEP-m (n = 7), NEP-s (n = 6).</p

Study 1: Distribution of HA expression in the hippocampus (A–D) and frontal cortex (E–H) following intracranial administration of rAAV vectors, detected using an anti-HA antibody.

<p>Panels A & E show NEP-n treated animals; panels B & F show NEP-m treated animals; panels C & G show NEP-s treated animals. Panels D & H show no positive staining in the contralateral uninjected left hippocampus and left anterior cortex, respectively. Scale bar = 120 µm.</p

Study 1: Congophilic staining is observed in mice throughout both ipsilateral hippocampus (A, B and C) and ipsilateral anterior cortex (D, E and F).

<p>Congophilic staining in the hippocampus of animals that received intracranial injections of rAAV- NEP-n (B) or NEP-s (C) is reduced compared to staining in those animals that received injections of control vector rAAV- NEP-m (A). Congophilic staining in the anterior cortex of mice that received intracranial injections of rAAV- NEP-s (F) or NEP-n (E) is also reduced compared to staining in mice that received control vector rAAV- NEP-m (D). Scale bar = 120 µm. Quantification of percent area of positive total Congophilic staining is shown in G (hemisphere ipsilateral to injection sites) and H (hemisphere contralateral to injection sites). NEP-n (n = 18), NEP-m (n = 15), NEP-s (n = 17). The (*) indicates significance compared to NEP-m with p<0.05.</p

Study 3: Aβ immunostaining is observed in mice throughout both the hippocampus (A, B and C) and anterior cortex (D, E and F).

<p>Aβ staining in the hippocampus of animals that received intracranial injections of rAAV- NEP-n (B) is reduced compared to staining in those animals that received injections of control vector rAAV- NEP-m (A). Aβ staining in the anterior cortex of mice that received intracranial injections of rAAV- NEP-n (E) or NEP-s (F) is also reduced compared to staining in mice that received control vector rAAV- NEP-m (D). Scale bar = 50 µm. Quantification of percent area of positive total Aβ staining is shown in and H. The (*) indicates significance compared to NEP-m mice with p<0.05; the (^∧) indicates significance compared to Tg control mice with p<0.05. The (#) indicates significance compared to NEP-m mice with p<0.01. Tg control (n = 9), NEP-n (n = 4), NEP-m (n = 7), NEP-s (n = 6).</p

Study 2: Aβ immunostaining is observed in mice throughout both the ipsilateral hippocampus (A, B and C) and ipsilateral anterior cortex (D, E and F).

<p>Aβ staining in the hippocampus of animals that received intracranial injections of rAAV- IDE-n (B) or IDE-s (C) is unchanged compared to staining in those animals that received injections of control vector rAAV- GFP (A). Aβ staining in the anterior cortex of mice that received intracranial injections of rAAV- IDE-n (E) or IDE-s (F) is also unchanged compared to staining in mice that received control vector rAAV- GFP (D). Scale bar = 120 µm. Quantification of percent area of positive staining is shown in the hippocampus (G) and in the anterior cortex (H). No significant differences were observed. n = 8/group.</p

Study 3: Congophilic staining is observed in mice throughout both the hippocampus (A, B and C) and anterior cortex (D, E and F).

<p>Congophilic staining in the hippocampus of animals that received intracranial injections of rAAV- NEP-n (B) is reduced compared to staining in those animals that received injections of control vector rAAV- NEP-m (A). Congophilic staining in the anterior cortex of mice that received intracranial injections of rAAV- NEP-n (E) or NEP-s (F) is also reduced compared to staining in mice that received control vector rAAV- NEP-m (D). Scale bar = 50 µm. Quantification of percent area of positive total Aβ staining is shown in G and H. The (*) indicates significance compared to NEP-m mice with p<0.05, the (^∧) indicates significance compared to Tg control mice with p<0.05, and the (°) indicates significance compared to Tg control mice with p<0.01. Tg control (n = 9), NEP-n (n = 4), NEP-m (n = 7), NEP-s (n = 6).</p