Matches in SemOpenAlex for { <https://semopenalex.org/work/W4306403486> ?p ?o ?g. }
- W4306403486 endingPage "2565" @default.
- W4306403486 startingPage "2548" @default.
- W4306403486 abstract "Alzheimer's disease (AD) patients present with symptoms such as impairment of insulin signaling, chronic inflammation, and oxidative stress. Furthermore, there are comorbidities associated with AD progression. For example, osteoporosis is common with AD wherein patients exhibit reduced mineralization and a risk for fragility fractures. However, there is a lack of understanding on the effects of AD on bone beyond loss of bone density. To this end, we investigated the effects of AD on bone quality using the 5XFAD transgenic mouse model in which 12-month-old 5XFAD mice showed accumulation of amyloid-beta (Aβ42) compared with wild-type (WT) littermates (n = 10/group; 50% female, 50% male). Here, we observed changes in cortical bone but not in cancellous bone quality. Both bone mass and bone quality, measured in femoral samples using imaging (micro-CT, confocal Raman spectroscopy, X-ray diffraction [XRD]), mechanical (fracture tests), and chemical analyses (biochemical assays), were altered in the 5XFAD mice compared with WT. Micro-CT results showed 5XFAD mice had lower volumetric bone mineral density (BMD) and increased endocortical bone loss. XRD results showed decreased mineralization with smaller mineral crystals. Bone matrix compositional properties, from Raman, showed decreased crystallinity along with higher accumulation of glycoxidation products and glycation products, measured biochemically. 5XFAD mice also demonstrated loss of initiation and maximum toughness. We observed that carboxymethyl-lysine (CML) and mineralization correlated with initiation toughness, whereas crystal size and pentosidine (PEN) correlated with maximum toughness, suggesting bone matrix changes predominated by advanced glycation end products (AGEs) and altered/poor mineral quality explained loss of fracture toughness. Our findings highlight two pathways to skeletal fragility in AD through alteration of bone quality: (i) accumulation of AGEs; and (ii) loss of crystallinity, decreased crystal size, and loss of mineralization. We observed that the accumulation of amyloidosis in brain correlated with an increase in several AGEs, consistent with a mechanistic link between elevated Aβ42 levels in the brain and AGE accumulation in bone. © 2022 American Society for Bone and Mineral Research (ASBMR)." @default.
- W4306403486 created "2022-10-17" @default.
- W4306403486 creator A5004332213 @default.
- W4306403486 creator A5012143262 @default.
- W4306403486 creator A5036296563 @default.
- W4306403486 creator A5066421732 @default.
- W4306403486 creator A5067638221 @default.
- W4306403486 creator A5091765205 @default.
- W4306403486 date "2022-11-01" @default.
- W4306403486 modified "2023-10-15" @default.
- W4306403486 title "Degradation of Bone Quality in a Transgenic Mouse Model of Alzheimer′s Disease" @default.
- W4306403486 cites W1480870442 @default.
- W4306403486 cites W1512881390 @default.
- W4306403486 cites W1755353237 @default.
- W4306403486 cites W1896856921 @default.
- W4306403486 cites W1904050321 @default.
- W4306403486 cites W1958698361 @default.
- W4306403486 cites W1965505631 @default.
- W4306403486 cites W1970472781 @default.
- W4306403486 cites W1971589882 @default.
- W4306403486 cites W1973913584 @default.
- W4306403486 cites W1981463613 @default.
- W4306403486 cites W1983773897 @default.
- W4306403486 cites W1986711635 @default.
- W4306403486 cites W1998307843 @default.
- W4306403486 cites W2008487250 @default.
- W4306403486 cites W2017568962 @default.
- W4306403486 cites W2022836308 @default.
- W4306403486 cites W2024608325 @default.
- W4306403486 cites W2030389395 @default.
- W4306403486 cites W2035302980 @default.
- W4306403486 cites W2035921184 @default.
- W4306403486 cites W2043335534 @default.
- W4306403486 cites W2049177176 @default.
- W4306403486 cites W2052766033 @default.
- W4306403486 cites W2053602366 @default.
- W4306403486 cites W2058682625 @default.
- W4306403486 cites W2058769842 @default.
- W4306403486 cites W2063938651 @default.
- W4306403486 cites W2065258689 @default.
- W4306403486 cites W2066749771 @default.
- W4306403486 cites W2071791622 @default.
- W4306403486 cites W2072195566 @default.
- W4306403486 cites W2088359126 @default.
- W4306403486 cites W2089248086 @default.
- W4306403486 cites W2090586279 @default.
- W4306403486 cites W2093799427 @default.
- W4306403486 cites W2112857078 @default.
- W4306403486 cites W2114991125 @default.
- W4306403486 cites W2125473951 @default.
- W4306403486 cites W2125606512 @default.
- W4306403486 cites W2130413565 @default.
- W4306403486 cites W2135148756 @default.
- W4306403486 cites W2142608062 @default.
- W4306403486 cites W2142996665 @default.
- W4306403486 cites W2148911867 @default.
- W4306403486 cites W2153501721 @default.
- W4306403486 cites W2166747071 @default.
- W4306403486 cites W2170644095 @default.
- W4306403486 cites W2173023862 @default.
- W4306403486 cites W2329659082 @default.
- W4306403486 cites W2341968115 @default.
- W4306403486 cites W2346226609 @default.
- W4306403486 cites W2401563407 @default.
- W4306403486 cites W2420952677 @default.
- W4306403486 cites W2463384721 @default.
- W4306403486 cites W2507233193 @default.
- W4306403486 cites W2513379432 @default.
- W4306403486 cites W2547969205 @default.
- W4306403486 cites W2600872530 @default.
- W4306403486 cites W2743585247 @default.
- W4306403486 cites W2750682079 @default.
- W4306403486 cites W2755017474 @default.
- W4306403486 cites W2784148496 @default.
- W4306403486 cites W2787250590 @default.
- W4306403486 cites W2788920791 @default.
- W4306403486 cites W2795712735 @default.
- W4306403486 cites W2808584356 @default.
- W4306403486 cites W2891837081 @default.
- W4306403486 cites W2897857173 @default.
- W4306403486 cites W2898009164 @default.
- W4306403486 cites W2902363090 @default.
- W4306403486 cites W2907801895 @default.
- W4306403486 cites W2916588181 @default.
- W4306403486 cites W2917819925 @default.
- W4306403486 cites W2921788352 @default.
- W4306403486 cites W2939054606 @default.
- W4306403486 cites W2944174704 @default.
- W4306403486 cites W2948490726 @default.
- W4306403486 cites W2949519242 @default.
- W4306403486 cites W2956714488 @default.
- W4306403486 cites W2961845320 @default.
- W4306403486 cites W3004362547 @default.
- W4306403486 cites W3040695438 @default.
- W4306403486 cites W3047411135 @default.
- W4306403486 cites W3087619526 @default.
- W4306403486 cites W3112628757 @default.
- W4306403486 cites W3124983389 @default.