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Neuropathological characterization of early onset Alzheimer disease associated with the V717L APP mutation
Author(s) -
Spina Salvatore,
Murrell Jill R,
Hake Ann M,
Epperson Francine,
Vidal Ruben,
Farlow Martin R,
Ghetti Bernardino
Publication year - 2008
Publication title -
the faseb journal
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.709
H-Index - 277
eISSN - 1530-6860
pISSN - 0892-6638
DOI - 10.1096/fasebj.22.1_supplement.707.8
Subject(s) - senile plaques , pathology , immunohistochemistry , cerebral amyloid angiopathy , alzheimer's disease , amyloid (mycology) , angiopathy , proband , antibody , biology , mutation , medicine , disease , dementia , gene , immunology , genetics , endocrinology , diabetes mellitus
Objective: To report the neuropathological findings associated with the V717L mutation in the Amyloid Precursor Protein ( APP ) gene. Methods: The proband presented with short‐term memory loss at age 35 and died at age 44. His brain was processed for histology and immunohistochemistry (IHC). Aβ IHC was carried out using antibodies recognizing Aβ3–7, AβN3pE, Aβ10–16, Aβ17–24, AβN‐40 and AβN‐42. Results: Neuritic plaques (CERAD stage C) were abundant in the intermediate neocortical layers. Abundant diffuse Aβ deposits were observed in the remaining cortical layers as well as in the subpial zone. Mild amyloid angiopathy was seen, predominantly in penetrating vessels. Braak VI‐tau pathology was observed, particularly affecting layer V and VI. Neuritic plaques were immunoreactive against the full panel of Aβ antibodies except for the anti‐AβN‐40. Diffuse deposits contained AβN‐42 species but did not react with antibodies recognizing epitopes located before position 11. Conclusions: Our data suggest a heterogeneous involvement of the cortical layers by the deposition of Aβ species with specific immunohistochemical pattern. They also suggest that diffuse deposits, in the upper and lower cortical layers, are composed by N‐terminally truncated Aβ species. Supported by AG10133 and Alzheimer's Association.