Fig 1: Changes in mitophagy biomarkers across AD continuum. Violin plots of ANCOVA analyzes (A–D) levels of mitophagy markers PINK1, BNIP3L, and TFEB in biomarker-defined individuals. (A) CSF PINK1 showed higher levels in AD dementia compared to MCI-AD and CU groups. (B) Serum PINK1 showed higher levels in AD dementia compared to MCI-AD group. (C) Serum BNIP3L showed higher levels in AD dementia compared to MCI-AD group. (D) Serum TFEB showed lower levels in AD dementia compared to MCI-AD and CU groups. Notes: Data were adjusted for sex and age. *** = p < .001, ** = p < .01, * = p < .05. Abbreviations: AD, Alzheimer disease; MCI, mild cognitive impairment; CSF, cerebrospinal fluid; CU, cognitively unimpaired.
Fig 2: Changes of mitophagy proteins in CSF and serum in clinical cohort. Violin plots of ANCOVA analyses (A–F) of levels of mitophagy biomarkers PINK1, ULK1, BNIP3L, and TFEB in biomarker-defined individuals. (A) CSF PINK1 showed lower levels in both FTLD dementia and FTLD-MCI compared to AD dementia and AD-MCI groups. It also showed higher levels in AD dementia compared to AD-MCI and CU. (B) Serum PINK1 showed lower levels in FTLD dementia compared to AD dementia and higher levels in AD dementia compared to AD-MCI. (C) CSF ULK1 showed higher levels in FTLD-MCI compared to AD dementia and AD-MCI groups. It also showed lower levels in AD-MCI compared to CU. (D) Serum ULK1 showed higher levels in FTLD dementia compared to AD-MCI and CU. (E) Serum BNIP3L showed higher levels in AD dementia compared to AD-MCI. (F) Serum TFEB showed higher levels in FTLD dementia compared to AD dementia, AD-MCI and CU groups. It also showed higher levels in FTLD-MCI compared to AD dementiaNotes: Data were adjusted for sex and age. *** = p <.001, ** = p <.01, * = p <.05. Abbreviations: AD, Alzheimer’s disease; FTLD, frontotemporal lobar degeneration; MCI, mild cognitive impairment; CSF, cerebrospinal fluid; CU, cognitively unimpaired
Fig 3: Changes of mitophagy proteins in the clinical spectrum of FTLD. Violin plots of ANCOVA analyses (A-F) of levels of mitophagy biomarkers PINK1, ULK1, BNIP3L, and TFEB in the clinical spectrum of FTLD. (A) CSF PINK1 showed lower levels in bvFTD compared to CU and was almost significantly lower in bvFTD compared to svPPA. (B) Serum PINK1 levels did not show any differences among the groups. (C) CSF ULK1 levels did not show any differences among the groups. (D) Serum ULK1 levels did not show any differences among the groups. (E) Serum BNIP3L levels did not show any differences among the groups. (F) Serum TFEB showed higher levels in nvPPA compared to CUNotes: Data were adjusted for sex and age. ***p <.001; **p <.01; *p <.05. Abbreviations: AD, Alzheimer’s disease; FTLD, frontotemporal lobar degeneration; MCI, mild cognitive impairment; CSF, cerebrospinal fluid; CU, cognitively unimpaired
Fig 4: Changes of mitophagy biomarkers according to AT(N) profile. Violin plots of ANCOVA analyses (A-F) of levels of mitophagy biomarkers PINK1, ULK1, BNIP3L, and TFEB according to AT(N) profile. (A) CSF PINK1 showed lower levels in the A-T-N- group compared to all the other groups. It also showed lower levels in the A + T-N- group compared to the A + T + N + group. (B) Serum PINK1 levels did not show any differences among the groups. (C) CSF ULK1 showed higher levels in the A-T + N + group compared to the A-T-N-, A + T-N-, A + T + N-, and A + T + N + groups. It also showed lower levels in the A + T-N- group compared to the A-T + N-/T-N + and A + T + N + groups. (D) Serum ULK1 levels did not show any differences among the groups. (E) Serum BNIP3L levels did not show any differences among the groups. (F) Serum TFEB showed higher levels in the A-T-N- group compared to the A + T-N- and A + T + N + groupsNotes: Data were adjusted for sex and age. *** p <.001; **p <.01; *p <.05. Abbreviations: AD, Alzheimer’s disease; FTLD, frontotemporal lobar degeneration; MCI, mild cognitive impairment; CSF, cerebrospinal fluid; CU, cognitively unimpaired
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