Amyloid-β42 alters apolipoprotein E solubility in brains of mice with five familial AD mutations

Katherine Lynn Youmans*, Steffi Leung, Juan Zhang, Erika Maus, Kathleen Baysac, Guojun Bu, Robert Vassar, Chunjiang Yu, Mary Jo LaDu

*Corresponding author for this work

Research output: Contribution to journalArticlepeer-review

53 Scopus citations


Amyloid plaques composed of the 42 amino acid form of amyloid-β peptide (Aβ42) are a pathological hallmark of Alzheimer's disease (AD), but soluble and intraneuronal Aβ42 are the more proximal causes of synaptic dysfunction and neurotoxicity. Apolipoprotein E (apoE) modulates this disease process, as inheritance of the e{open}4 allele of the apoE gene is the primary genetic risk factor for AD. To address the solubility of Aβ42 and apoE, the 5xFAD-specific extraction profile for Aβ42 was optimized, a protein extraction protocol was optimized in the presence of minimal to extensive Aβ42 pathology. Sequential extractions with TBS, TBS. +. Triton X-100 (TBSX), and guanidine-HCl (GuHCl) or formic acid (FA) were used with tissue from young and old wild type or mice expressing 5 familial AD mutations (5xFAD), in disease-susceptible or -resistant brain regions. In older 5xFAD mice, the extraction of insoluble Aβ42 and m-apoE protein was increased with FA compared to GuHCl. The 5 FAD mutations significantly increase production of Aβ42, recapitulating AD-like pathology at a greatly accelerated rate. Consistent protein extraction and the specificity of extractions for soluble or membrane-associated proteins were demonstrated. Age-dependent increases in Aβ42 were observed in all extraction fractions, particularly in the cortex and hippocampus. In both young and old 5xFAD mice, Aβ42 is TBS- or GuHCl-soluble. While in WT mice m-apoE is TBSX-soluble, in 5xFAD mice m-apoE is TBS- or GuHCl-soluble. Thus, the 5xFAD-specific extraction profile of Aβ42 paralleled that of m-apoE. As now characterized, this method identifies the extraction profile for disease relevant apoE and Aβ in the brain, both normal or modified due to neuropathological processes.

Original languageEnglish (US)
Pages (from-to)51-59
Number of pages9
JournalJournal of Neuroscience Methods
Issue number1
StatePublished - Mar 15 2011


  • 5xFAD
  • Alzheimer's disease
  • ApoE
  • Detergent
  • Solubility

ASJC Scopus subject areas

  • General Neuroscience


Dive into the research topics of 'Amyloid-β42 alters apolipoprotein E solubility in brains of mice with five familial AD mutations'. Together they form a unique fingerprint.

Cite this