Table 2.

CSF Aβ isoform concentrations and selected model kinetic parameters.

	Non-carriers (n=12)	Mutation carriers (n=11)	P-valuesa
Production rate, ng/h (e.g. C99 pool size × kAβ42)			Mutation status	PIB MCBP score
Aβ38	106[41]	111[50]	0.603	0.571
Aβ40	418±83	452±138	0.621	0.901
Aβ42	57[19]	67[35]	0.038	0.769
Aβ38:Aβ40 ratio	0.267[0.021]	0.252[0.052]	0.692	0.179
Aβ42:Aβ40 ratio	0.140±0.011	0.174±0.020	9×10−5	0.312
Percentage of flux going to exchange (%)b			Mutation status	PIB status
Aβ38	9.8±16.6	0c	0.190	0.376
Aβ40	7.8±13.9	1.2±4.1	0.316	0.249
Aβ42	5.8±11.5	50.8±57.6	0.004	0.001
Permanent loss of soluble Aβ to all fates (fractional turnover rate, FTR) (pools/h) (e.g. v42+kCSF)			Mutation status	PIB MCBP score
Aβ38	0.144±0.046	0.124±0.049	0.802	0.054
Aβ40	0.156[0.055]	0.109[0.035]	0.990	0.024
Aβ42	0.147[0.049]	0.198[0.086]	0.065	0.548
Aβ38:40 ratio	0.964±0.038	1.013±0.047	0.157	0.115
Aβ42:40 ratio	0.942±0.080	1.553±0.382	0.0016	0.0003
CSF concentration by IP-MS (ng/mL)			Mutation status	PIB MCBP score
Aβ38	2.05[0.69]	1.82[1.00]	0.296	0.105
Aβ40	7.15±1.80	7.79±1.89	0.199	0.272
Aβ42	1.01[0.39]	0.80[0.52]	0.537	0.007
Aβ38:Aβ40 ratio	0.272±0.014	0.256±0.053	0.803	0.068
Aβ42:Aβ40 ratio	0.149±0.013	0.121±0.042	0.720	0.003

Parameters were determined based on the best-fit to a compartmental model of Aβ turnover and production. Outcomes were compared by mutation status using ANOVA after adjusting for fibrillar amyloid deposition by treating PIB MCBP score as a covariate. Kinetic parameters are identified with terminology (Fig. 2). P < 0.05 in bold.

^aP-values by ANOVA based on mutation status with PIB MCBP score as a covariate.

^bAnalyzed by non-parametric Mann-Whitney U test due to non-normal distribution, based on mutation status and PIB status (rather than PIB MCBP score).

^cNo exchange observed in any subject.