Fig. 1.

Increased levels and altered subcellular distribution of LAMP1-positive endolysosomes in the AD brain. (A,C) Representative images showing the accumulation and swelling of LAMP1-positive vesicles in cells of the CA1 (A) and CA3 (C) regions of hippocampal sections of AD (n=10) and control cases (n=10). Scale bars: 20 µm. Detailed sections of single neurons are shown in bottom panel of C. Scale bars: 5 µm. (B) Surface-rendered 3D reconstruction of LAMP1-positive vesicles in a morphologically identified CA1 pyramidal neuron of an AD patient and control. Scale bars: 10 µm. (D,E) Quantification of LAMP1 intensity in the CA1 region (D) and specifically in the perinuclear area (E) from n=6 AD cases and n=8 control cases with 2–5 representative images analysed for each case, together analysing n=26 control images and n=26 AD images. (F) Quantification of the number of enlarged LAMP1 immunoreactive vesicles per neuron in the CA3 region. (G) Representative images showing increased LAMP1 immunoreactivity in cells of the CA1 region accumulating PHF-1 immunoreactive tau in AD patients (n=10, right) and control (n=10, left), and areas of AD CA1 with little PHF1 immunoreactive tau (middle). (H) Representative image of LAMP1 localisation to senile plaques decorated with PHF-1 immunoreactive tau (n=10 AD cases). (I) Western immunoblot analysis of temporal cortex membrane fractions (n=6) showing a trend towards increased LAMP1 levels in AD patients compared with controls (n.s.). LiCor total protein stain was used to ensure equal loading. (J) Quantification of LAMP1 immunoblot data. Data are expressed as mean±s.e.m. *P<0.05; **P<0.01 (unpaired two-tailed Student's t-test).