Neuropathological changes associated with aberrant cerebrospinal fluid p-tau181 and Aβ42 in Alzheimer’s disease and other neurodegenerative diseases

Table 1 Group characteristics according to neuropathologic diagnosis

	AD	PD(D)/DLB	Primary tauopathy	TDP proteinopathy	Other	Multiple comparison p values	Total
n	22	26	30	16	33	Multiple comparison p values	127
Subtype (n)	AD 22	DLB 11, PDD 10, PD 5	PSP 18, CBD 4, PiD 1, DG/AGD 7	ALS ± FTD 12, FTLD-TDP 4	CVD 11, MSA 4 SCD 3, CJD 2 other 13
Age at LP (years)	77.9 ± 7.9	77.9 ± 7.3	78.1 ± 6.3	76.3 ± 5.9	72.2 ± 12.6	0.045* (F = 2.5)	76.2 ± 9.0
LP to ELISA (days)	7 (2–20)	16 (9–27)	22 (8–54)	12 (7–55)	18 (9–41)	0.27 (F = 1.3)	17 (7–44)
LP to autopsy (days)	1107 (363–2538)	860 (177–1948)	556 (172–1277)	249 (183–446)	379 (80–1408)	0.66 (F = 0.6)	623 (170–1620)
Sex (female, %)	40.9%	42.3%	36.7%	62.5%	33.3%	0.41	40.9%
APOE ε4 carrier	59.1%	19.2%	20.7%	26.7%	12.9%	0.0047**	26.0%
ADNC
none	0	4	6	4	11		25
low	0	18	18	11	18		65
intermediate	8	4	6	1	4		23
high	14	0	0	0	0		14
CSF biomarkers
Aβ42 results	22/22 (100%)	26/26 (100%)	30/30 (100%)	16/16 (100%)	33/33 (100%)	1	127/127 (100%)
Aβ42 (pg/mL)	258 ± 111	605 ± 317	460 ± 262	537 ± 233	601 ± 324	< 0.001† (F = 6.7)	501 ± 294
p-tau181 results	14/22 (63.6%)	16/26 (62%)	18/30 (60%)	12/16 (75%)	12/33 (36.4%)	0.73	72/127 (56.7%)
p-tau181 (pg/mL)	79.4 ± 34.6	41.9 ± 12.1	38.9 ± 20.1	44.3 ± 14.7	39.2 ± 9.4	< 0.001† (F = 10.1)	48.4 ± 25.1
t-tau results	22/22 (100%)	26/26 (100%)	30/30 (100%)	16/16 (100%)	32/33 (97.0%)	1	126/127 (99.2%)
t-tau (pg/mL)	577 ± 354	146 ± 87	140 ± 118	231 ± 136	266 ± 255	< 0.001† (F = 16.4)	261 ± 261

Abbreviations Aβ42, amyloid-beta 1–42; AD, Alzheimer’s disease; ADNC, AD neuropathologic change; AGD, argyrophilic grain disease; ALS, amyotrophic lateral sclerosis; APOE, apolipoprotein E CBD; corticobasal degeneration; CJD, Creutzfeldt-Jakob disease; CSF, cerebrospinal fluid; CVD, cerebrovascular disease; DG, dementia with grains; DLB, dementia with Lewy bodies; ELISA, enzyme-linked immunosorbent assay; FTD, frontotemporal dementia; FTLD-TDP, frontotemporal lobe degeneration with TDP-43 pathology; LP, lumbar puncture; MSA, multiple system atrophy; PD(D), Parkinson’s disease (with dementia); PiD, Pick’s disease; PSP, progressive supranuclear palsy; p-tau181, tau phosphorylated at threonine 181; SCD, spinocerebellar degeneration; TDP-43, TAR DNA-binding protein 43; t-tau, total tau. * Post-hoc Tukey test showed no significant difference between groups. ** Pairwise comparison showed a significantly higher frequency in AD compared to Other group, and a higher trend in AD compared to Primary tauopathy group (p = 0.065) and PD(D)/DLB group (p = 0.063). † Plots and results of post-hoc comparisons are shown in Supplementary Fig. 1

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