TABLE 2.

Summary of published research, comparing AD biomarkers in Black and non‐Hispanic White adults

Authors	Study design	Participants	AD biomarker(s)	Findings	Conclusions
Gottesman et al. (2016) a	Subset of participants recruited from population‐based study. Cross‐sectional analysis.	Participants’ race: 141 Black; 181 White Mean age (SD) in years: 75.9 (5.4) Ethnicity not reported Compared to Whites, Black participants had lower MMSE scores, intercranial volumes, and greater proportion had HTN. Diagnostic categories included: MCI and HC	[18]Florbetapir PET; global cortical amyloid from 9 ROIs provided dichotomous outcome of Amyloid positive v. negative (SUVR ≤ 1.2); WMH measured with MRI	Black participants had higher odds of beta amyloid positive status than Whites (OR = 2.08) Adjusting for vascular risk factors did not change odds ratio No racial differences in APOE ε4 associated increase odds of amyloid positive status	Presence of vascular risk factors in late life does not account for racial differences in cortical amyloid. Authors considered whether sociocultural factors could account for observed differences, but dismissed as unlikely. Proposed differences in metabolomic or genetic factors may contribute to differences between.
Howell et al. (2017)	Convenience sample recruited from ADC, clinic and community outreach events. Cross‐sectional analysis.	Participants’ race: 65 Black; 70 White Mean age in years: ∼70 Ethnicity not reported Compared to Whites, greater proportion of Black participants had HTN and DM. Diagnostic categories included: AD dementia, MCI, and HC	CSF levels of Aβ42, Aβ40, Aβ42/Aβ40, t‐tau, p‐tau181, t‐tau/Aβ42, p‐tau181/Aβ42 and NfL; and WMH and HV measured with MRI	Racial differences in AD biomarkers only observed in HC participants CSF Aβ40, t‐tau, and p‐tau181 lower in Black HCs comparted to White HCs No racial differences in CSF Aβ42 or NfL or in MRI HV or WMH Although similar levels of WMH were observed, found an interaction between race and WMH effects on cognition ‐ effect potentiated in Black individuals.	Considered several possible reasons for racial differences in CSF AD biomarkers. Misdiagnosis (White being HC) and differences in level of neurodegeneration were considered, but dismissed because amyloid levels were similar between racial groups. Also examined whether vascular disease or comorbid neuro‐pathologies may explain observed differences, finding no support for either theory. Concluded difference may be due to potentiated effects of WMH on cognition observed for Black individuals.
Garrett et al. (2019)	Case‐control, convenience sample of participants enrolled in B‐SHARP, recruited from an ADC. Cross‐sectional analysis.	Participants’ race: 152 Black; 210 White Mean age in years: ≈63–70 Ethnicity not reported Compared to Whites, Black participants were older; had lower education levels, MoCA scores, and mean HV; higher BMI; were less likely to demonstrate cognitive impairment on CDR scale or report a family history of AD; and greater proportion had HTN and DM. Diagnostic categories included: HC and MCI	CSF levels of Aβ42, Aβ40, t‐tau, P‐tau181, t‐tau/Aβ42, and P‐tau181/Aβ42; and HV measured with MRI; and ROC analyses with AUC	Racial differences in AD biomarkers only observed in participants with MCI CSF t‐tau and P‐tau181 lower in Black participants with MCI compared to Whites with MCI CSF Aβ40 concentration were higher in Black participants with MCI than for Whites with MCI; no differences in HCSF Aβ42 Ratios of CSF biomarkers (t‐tau/Aβ42, and p‐tau181/Aβ42) also lower in Black participants with MCI compared to Whites with MCI HV similar between racial groups overall, but non‐significant pattern observed with lower HV in HC Black participants and higher HV in Black participants with MCI compared to Whites For ROC analyses, AUC, and sensitivity and specificity estimates lower for Black participants than Whites	Differences in CSF biomarkers for AD were not accounted for by differences in cognitive performance, hippocampal neurodegeneration or vascular disease risk factors. Proposed possible contributions from other neuropathologies, i.e., mixed pathology. Also hypothesized that groups exhibited differences in cognitive reserve, with Whites having greater reserve than Black participants. Based on finding of ROC analyses, authors recommended caution when using cut‐off scores to characterize AD biomarker status across races.
Morris et al. (2019)	Convenience sample recruited from ADC. Cross‐sectional analysis.	Participants’ race: 173 Black; 1082 White Mean age (SD) in years: 70.8 (9.9) Ethnicity reported for Whites (all non‐Hispanic) Compared to Whites, Black participants were less likely to be male and to report a family history of AD. Black participants had lower educational attainment, and higher BMI and HbA1c values than Whites. CDR pattern differed within the mildly impaired range: A greater proportion of Black participants obtained a score of one compared to Whites who demonstrated a larger number of CDR = 0.5. Diagnostic categories included: HC, MCI, and AD dementia	HV measured with MRI (N = 1032 [13.9% Black]); partial volume corrected PET PIB SUVR (N = 569 [12.9% Black]); CSF levels of Aβ42, Aβ40, t‐tau, p‐tau181 (N = 903 [9.6% Black])	Black and White participants showed similar HV loss with age, but Black individuals in general had smaller HVs. The latter finding would observed to occur only in those with a family history of AD No differences between Black and White participants was observed in PET Amyloid measurements CSF Aβ42 levels were similar between racial groups CSF t‐tau and p‐tau181 were lower in Black than White participants. Significant interaction with APOE ε4 carrier status was also noted, such that Whites who were APOE ε4 positive demonstrated higher CSF t‐tau and p‐tau181 than Black individuals who were APOE ε4 positive	CSF tau level differences suggesting decreased neuropathology in Black participants compared to Whites were hypothesized to be related to a differential effect of the APOE ε4 carrier status, such that the gene shows a closer association with AD in Whites than Black participants. In contrast, in those with a family history of AD, HV were smaller in Black than White participants. Based on the similarities between racial groups in CSF amyloid levels and PET amyloid deposition, authors propose that the disease presents with an “identical AD biosignature” across the two groups. Rather, race was hypothesized to modify risk and expression of the disease.
Meeker et al. (2020)	Convenience sample recruited from ADC. Cross‐sectional analysis.	Participants’ race: 131 Black; 685 White Mean age in years: ≈71.45 Ethnicity not reported Compared to Whites, Black participants had lower educational attainment, higher BMI, higher systolic blood pressure, higher polygenic and risk scores for AD. Diagnostic categories included: HC	PET amyloid imaging: [11C] (PiB) or [18F]‐Florbetapir (AV45); PET tau imaging: [18F]‐Flortaucipir (AV1451)38 with SUVRs calculated for the 80 to 100‐minute post‐injection window. Brain volume atrophy in AD signature regions with structural MRI and resting state functional connectivity BOLD imaging.	No racial differences in PET amyloid deposition No racial differences in tau PET accumulation Black participants had smaller AD signature volume and higher WMH compared to Whites. No racial differences were observed for resting state functional connectivity	Greater cerebral volume loss in Black participants compared to whites reflect both direct and indirect contributors. Racial differences comprised lower education levels and higher polygenic risk for AD among Black participants.
Kumar et al. (2020)	Convenience sample recruited from ADC. Cross‐sectional analysis.	Participants’ race: 30 Black; 50 White Mean age: ≈59.1 years Ethnicity not reported Compared to Whites, Black participants displayed lower income despite similar education, poorer vascular health and fewer hours of sleep. Diagnostic categories included: HC with at least one biological parent with AD	CSF levels of t‐tau, p‐tau, Aβ42; vascular ultrasound of PWV, FMD, EndoPAT;	Black participants displayed lower CSF t‐tau and p‐tau Black participants showed borderline lower Aβ1‐40 and lower Aβ1‐38 compared to Whites Black participants performed more poorly on all cognitive measures, with significant differences on MoCA, Trails B, delayed word recall and naming. Race significantly modified relationship between Trail B and t‐tau and p‐tau after adjusting for age, sex, education, and APOE ε4 status	Lower levels of tau in Black participants than Whites suggests that AD neuropathology begins during middle age. White participants displayed higher scores on all cognitive tests than Black individuals, suggesting that cognitive tests may have implicit cultural biases favoring Whites. As race modified relationship between tau and executive function such that small changes in tau resulted in worse cognition among Black participants compared to Whites. neuropathology of tau deposition may differ in Black participants. Existing cut‐off values for CSF biomarkers may be inappropriate for Black patients.
Deters et al. (2021)	Convenience sample recruited from A4 study. Cross‐sectional analysis.	Participants’ race: 144 Non‐Hispanic Black; 3689 Non‐Hispanic White Mean age: ≈71.22 years Ethnicity was reported Compared to White participants, Black participants had lower educational attainment. There was a higher proportion of APOE ε2/3 genotype in Black compared to white participants. Black participants were more likely to be screened out of the study in part due to worse scores on neuropsychological testing Diagnostic categories included: HC	PET amyloid imaging; raw continuous amyloid SUVR; participants were classified into amyloid groups using a cut‐point of ≥1.17.	Black participants had lower levels of PET amyloid positivity and lower continuous levels of amyloid compared to Whites There was a significant interaction between APOE ε4 and race such that Black individuals with APOE ε4 positivity had lower SUVR units than APOE ε4 positive Whites High level of African ancestry within Black participants was associated with reduced amyloid levels independent of APOE ε4 status APOE ε2 did not appear protective in Black participants Black participants reported lower alcohol consumption, greater cardiovascular risk factors and lower self report of multiple medical conditions.	Less amyloid among Black participants suggests other risk factors may contribute to AD dementia among Black participants, such as vascular risk factors, TDP43 pathology, other age‐related pathologies, and other social determinants of health, e.g., increased lifespan exposure to stress. Representing an important gap in the literature, it is unknown whether PET measures of AD pathology equally predict future progression to dementia in Black participants compared to Whites. Baseline neuropsychological tests may not accurately capture true cognitive ability in Black participants, instead reflecting biases and inadequate norms. The authors emphasized that race is a social construct predominantly used in the United States and current data may not adequately its effect on risk of AD and amyloid.

Abbreviations: A4, Anti‐Amyloid Treatment in Asymptomatic Alzheimer's Disease; Aβ, amyloid beta; AD, Alzheimer's disease; ADC, Alzheimer's Disease Center; ADI, Area Disadvantage Index; APOE ε4, ε4 allele of the apolipoprotein E gene; AUC, area under the curve; BMI, body mass index; BOLD, blood oxygen level dependent; B‐SHARP, Brain Stress Hypertension and Aging Research Program; CDR, Clinical Dementia Rating; CSF, cerebrospinal fluid; DM, diabetes; EndoPAT, pulsatile arterial tonometry; FMD, flow‐mediated vasodilation; HbA1c, hemoglobin A1c test; HC, healthy control; HTN, hypertension; HV, hippocampal volume; MCI, mild cognitive impairment; MMSE, Mini‐Mental State Examination; MoCA, Montreal Cognitive Assessment; MRI, magnetic resonance imaging; NfL, neurofilament light chain; OR, odds ratio; PET, positron emission tomography; PiB, Pittsburgh compound B; SES, socioeconomic status; p‐tau181, tau phosphorylated at threonine 181; PWV, pulse wave velocity; ROI, regions of interest; ROC, receiver operating curves; SD, standard deviation; SUVR, standardized uptake value ratio; TDP43, TAR DNA‐binding protein 43; t‐tau, total tau; WMH, white matter hyperintensities.

^a Gottesman et al. (2017) also included Black participants. However, rather than contrasting AD biomarker in Black and White participants, study compared relationship between vascular risk in midlife and amyloid deposition, examining whether the relationship differed by race.

Notes: Overall, AD biomarkers measured in these studies behaved as expected, for example, increasing age and clinical symptoms, and APOE ε4 carrier status were associated with elevated PET amyloid levels, decreased CSF Aβ42, increased CSF T‐tau, P‐tau181, and neurodegeneration