Fig 1: Co-localization between SORL1 and APP in postmortem brain as detected by in situ PLA. a-c shows representative sections of the three groups; a Ctrl = controls, b sAD = sporadic AD, and c PED.25 = affected family member from PED.25. d The mean number of PLA dots/neuron, represented as horizontal bars (−), was quantified in pyramidal neurons in frontal cortex from controls (n = 4), sporadic AD (n = 4) and PED.25 (n = 2). A minimum of 100 neurons was quantified from every individual. The individual values are represented as filled squares (■)
Fig 2: Schematic picture of the SORL1 protein adapted from Verheijen et al., presenting the location of SORL1 variants that are “likely pathogenic” (in bold) and variants of “uncertain significance”, also see Table 2. Functional domains are based on Uniprot information (Q92673), and numbering of variations are based on NM_003105.5 (cDNA) and NP_003096 (protein). Below are lines corresponding to the epitopes used to generate the respective antibodies (MAB5699, AF5699, 612633 and ab190684) applied in the study. Vps10p: vacuolar protein sorting 10 domain; LDLR class B: low-density lipoprotein-receptor class B repeats; EGF: epidermal growth factor-like domain; LDLR class A: low-density lipoprotein-receptor class A domain; Fibronectin III: Fibronectin type-III domain; TM: transmembrane domain
Fig 3: Pedigree of family PED.25. The family segregates the SORL1 variant c.3907C > T (p.Arg1303Cys) in two generations. Individuals included in the whole-exome sequencing (WES) are marked with an *. The genetic status for variant c.3907C > T is indicated “carrier” for heterozygotes, “wildtype” when absent, and “unknown” if DNA was unavailable. Diagnosis refers to the clinical diagnosis. Onset refers to first observation of dementia symptoms, and APOE indicates the ε-alleles. Neuropath indicates the post mortem neuropathological diagnosis. The age at last known affection status of individuals still alive is indicated in parenthesis
Fig 4: Pedigree of family PED.1499. The family segregates the SORL1 variant c.5195G > C (p.Gly1732Ala) in one generation. Individual (II:2) included in the EU EOD case-control study is marked with an *. The genetic status for variant c.5195G > C is indicated “carrier” for heterozygotes, “wildtype” when absent, and “unknown” if DNA was unavailable. NPH = normal pressure hydrocephalus. Onset refers to first observation of dementia symptoms, and APOE indicates the ε-alleles. The age at last known affection status of individuals still alive is indicated in parenthesis
Fig 5: Immunohistochemical localization of SORL1 in postmortem brain material from controls, sporadic AD and PED.25. Representative pictures from control (a-c), sporadic AD (d-f) and PED.25 (g-i) in the CA1 region of hippocampus (a-b, d-e, g-h) and subcortical white matter in frontal cortex (c, f, i) using two different SORL1 antibodies, AF5699 (a, d, g) and MAB5699 (b-c, e-f, h-i). The AF5699 SORL1 antibody showed an intense immunoreactivity of extracellular SORL1 aggregates in PED.25 (arrows in g). Arrowheads indicate strong SORL1 immunoreactivity (MAB5699) in glial cells in grey (h) and white matter (i) in the affected member from PED.25. Scalebar: 50 μm. Ctrl = control, sAD = sporadic AD, PED.25 = affected family member II:6
Supplier Page from Abcam for Anti-SorLA/SORL1 antibody [EPR14670]