The apolipoprotein E4 (APOE4) allele is associated with an early age of onset of the nonfamilial form of Alzheimer disease (AD) and with increased 8 protein amyloid deposition in the brain. These two observations may both arise from an effect of the apoE family of proteins on the rate of in vivo amyloidogenesis. We report here that apoE3, the common apoE isoform, is an in vitro amyloid nucleation inhibitor at physiological concentrations. A significant delay in the onset of amyloid fibril formation by the ,3-amyloid protein of AD (181-40) was observed at a low apoE3 concentration (40 nM), corresponding to an apoE3/13 protein molar ratio of 1:1000. The inhibitory activity of a proteolytic fragment of apoE3, containing the N-terminal 191 amino acids, is comparable to the native protein, whereas the C-terminal fragment has no activity. ApoE4 is equipotent or slightly less potent than apoE3, which may be due to its inability to form a disulfide dimer, since the apoE3 dimer is a significantly more potent nucleation inhibitor than apoE4. Neither apoE3 nor apoE4 inhibits the seeded growth of amyloid or affects the solubility or structure of the amyloid fibrils, indicating that apoE is not a thermodynamic amyloid inhibitor. We propose that the linkage between the APOE4 allele and AD reflects the reduced ability of APOE4 homozygotes to suppress in vivo amyloid formation.Amyloid plaque is an ordered, fibrous protein aggregate that is characteristic of the Alzheimer disease (AD) brain. The acceleration of amyloid deposition may be a primary event in AD (1, 2). Thus, endogenous factors that affect the rate of amyloid formation could play a significant role in the pathogenesis of AD (3, 4). The apolipoprotein E genotype (APOE) has recently been recognized as a susceptibility factor for AD (5-8). Three isoforms of apoE occur in the human population. They differ by single amino acid changes. APOE3 is the most common allele (0.78), followed by APOE4 (0.14) and APOE2 (0.07) (9). ApoE4 and apoE3 differ with respect to lipoprotein binding (10), but the two proteins are indistinguishable with respect to low density lipoprotein receptor binding (11). ApoE3 and apoE4 are distinguished by a single point mutation in a sequence of 299 amino acids (apoE3, C112; apoE4, R112) (12).TheAPOE4 allele correlates with an earlier age of AD onset (5) and an increased amount of cerebral amyloid plaque (13) at the time of death relative to the common APOE3 allele. (/3,,). Once the nucleus has formed, association becomes favorable (Kg >> 1) and is not inhibited by apoE. Exogenous seed fibrils will bypass the lag time and result in rapid growth that is not inhibited by apoE (see Fig. 2).

A new indolocabazole derivative possessing an extended aromatic core and solubilizing long aliphatic chains effectively self-assembles and crystallizes within the nanoscale channels to form single-crystal nanowires via a direct printing method from an ink solution. Single-crystal organic nanowire transistor arrays based on the π-extended indolocarbazole derivative exhibit an excellent hole mobility of 1.5 cm² V⁻¹ s⁻¹ and outstanding environmental stability.

[reaction: see text] N-Boc aryl hydrazines undergo Pd-catalyzed coupling reactions with aryl halides to provide N-Boc diaryl hydrazines in excellent yields. The resulting N-Boc diaryl hydrazines were directly oxidized with NBS/pyridine in CH(2)Cl(2) at room temperature to the azobenzenes.

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To date, Spiro-OMeTAD, which is an expensive organic compound, is used as the benchmark hole transporting materials (HTMs) in perovskite based solid state solar cells. Development of an inexpensive HTM and competitive performance to Spiro-OMeTAD is therefore significantly important for commercialization of perovskite cells. Herein, an indolocarbazole based small molecule derivative (C12-Carbazole) has been introduced as environmentally stable, cost effective and highly efficient HTM. In contrast to the power conversion efficiency of 9.62 % exhibited by the Spiro-OMeTAD based solid state solar cell, the C12-Carbazole based device under the same experimental conditions has demonstrated an enhanced power conversion efficiency of 11.26 %.The improved photovoltaic performance of the C12-Carbazole based device is attributed to the lowering of carrier recombination by better hole extraction ability of the C12-Carbazole, which has demonstrated remarkably higher hole mobility compared to Spiro-OMeTAD.