Received: 17 May 2022 Revised: 14 September 2022 Accepted: 10 October 2022

DOI: 10.1002/jca.22026

RESEARCH ARTICLE

Feasibility, safety, and tolerability of two modalities of

plasma exchange with albumin replacement to treat elderly
patients with Alzheimer's disease in the AMBAR study

Mercè Boada 1,2 | Dobri Kiprov 3 | Fernando Anaya 4 | Oscar L. Lo
pez 5 |

Laura Núñez 6 | Javier Olazara
n 7,8 | José Lima 9 | Carlota Grifols 6 |

6 | Regina Rohe 3 | Cristina Prieto-Ferna
Miquel Barcelo
ndez 10 |
Zbigniew M. Szczepiorkowski 11 | Antonio Pa
ez 6
1
Ace Alzheimer Center Barcelona - Universitat Internacional de Catalunya, Barcelona, Spain
2
Centro de Investigaci
on Biomédica en Red de Enfermedades Neurodegenerativas (CIBERNED), Instituto de Salud Carlos III, Madrid, Spain
3
Apheresis Care Group and Fresenius Medical Care, San Francisco, California, USA
4
Nephrology Service, Hospital General Universitario Gregorio Marañ

on, Madrid, Spain
5
Departments of Neurology and Psychiatry, University of Pittsburgh School of Medicine, Pittsburgh, Pennsylvania, USA
6
Alzheimer's Research Group, Grifols, Barcelona, Spain
7
Neurology Service, Hospital General Universitario Gregorio Marañ

on, Madrid, Spain
8
Memory Disorders Clinic, HM Hospitales, Madrid, Spain
9
American Red Cross Southern Blood Services Region, Atlanta, Georgia, USA
10
Medical Department, Banc de Sang i Teixits, Barcelona, Spain
11
Department of Pathology and Laboratory Medicine, Dartmouth Hitchcock Medical Center, Lebanon, New Hampshire, USA

Correspondence
Antonio P
aez, MD, Grifols, Alzheimer's
Research Group, Avinguda de la
Generalitat, 152-158, 08174 Sant Cugat del
Vallès, Barcelona, Spain.
Email: antonio.paez@grifols.com
Funding information
Grifols
Abstract
Background: In the Alzheimer Management by Albumin Replacement
(AMBAR) study, mild-to-moderate Alzheimer's disease (AD) patients were
treated with a plasma exchange (PE) program. Feasibility and safety of PE in
this specific population are poorly understood and were analyzed in detail in
this study.
Methods: Qualified patients were treated with 6 weeks of weekly conven-
tional therapeutic plasma exchange (TPE) with albumin replacement followed
by monthly low-volume plasma exchange (LVPE) for 12 months. The patients
were divided into four groups: placebo (sham PE treatment), low-albumin
(20 g), low-albumin + intravenous immunoglobulin (IVIG) (10 g), and high-
albumin (40 g) + IVIG (20 g). Adverse events (AEs) were recorded and ana-
lyzed for all PE treatment groups and PE modalities.
Results: PE procedure-related AEs were more common in the active treat-
ment groups (16.9% out of 1283 TPE and 12.5% out of 2203 LVPE were

This is an open access article under the terms of the Creative Commons Attribution-NonCommercial-NoDerivs License, which permits use and distribution in any
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© 2022 The Authors. Journal of Clinical Apheresis published by Wiley Periodicals LLC.

J Clin Apher. 2023;38:45–54. wileyonlinelibrary.com/journal/jca 45

46 BOADA ET AL.

associated with at least one AE, a similar rate than in other PE indications)
than in the placebo group (0.7% out of 1223 sham PE). Percentage of proce-
dures with at least one AEs was higher with central venous access compared to
peripheral venous access in all three active treatment groups (20.1% vs 13.1%,
respectively).
Conclusion: The TPE and LVPE procedures used in the AMBAR study on
mild-to-moderate AD population were as safe and feasible as in other thera-
peutic applications of PE or routine plasmapheresis.

KEYWORDS
adverse event, Alzheimer's disease, apheresis, cognition, dementia, intravenous
immunoglobulin, plasma exchange, plasmapheresis, venous access

1 | INTRODUCTION (89%) is bound to albumin at one to one ratio.16 Based on

With the growth of older populations around the world,
increasing incidence of dementia is a prominent public
health problem. In 2020, an estimated 55 million people
were living with dementia worldwide.1 The number of
people suffering from dementia is projected to increase to
131.5 million by 2050.2 Sixty to eight percent of these
cases of dementia are classified as Alzheimer's disease
(AD).3 AD is characterized by memory impairment, cog-
nitive decline, psycho-affective and behavioral disorders,
and loss of communication and spatial skills.4 In addi-
tion, microscopic changes have been observed (postmor-
tem) in the brains of AD patients. Amyloid plaques and
neurofibrillary tangles are found in the brains of AD
patients and both are associated with the functional
decline and death of neuronal cells. The plaques are
made up of amyloid β peptides (Aβ), while the neurofi-
brillary tangles are composed of phosphorylated tau
proteins.5,6
At present, standard treatment for AD is symptom-
atic, consisting of acetylcholinesterase inhibitors and N-
methyl-D-aspartate receptor antagonists.7 However,
although new treatments of AD directed toward affecting
the underlying mechanisms of the disease—specifically
Aβ accumulation and deposition—have met to date with
little success,8-10 recent studies with anti-Aβ antibodies
are contributing to the understanding of the Aβ patho-
physiology associated with reduction of Aβ plaques.11-14
The Alzheimer Management by Albumin Replacement
(AMBAR) study has taken a new, unique approach to
AD by attempting to alter the disease process through
plasma exchange (PE) with albumin replacement.15
Aβ is found in the plasma and cerebrospinal fluid
(CSF) as a product of normal cellular metabolism. In both
compartments, Aβ is highly protein-bound and albumin is
the predominant protein. The majority of Aβ in plasma
the finding that Aβ in the CSF is in equilibrium with Aβ in
plasma,17 removal of Aβ (bound to albumin) by PE would
draw Aβ out of the CSF to re-establish Aβ levels in
plasma.18-21 In the AMBAR study, PE was performed by
replacement with therapeutic Aβ-free albumin22 to not
only maintain osmotic pressure and prevent hypovolemia23
but to provide new potential binding sites for plasma Aβ
and further sequestration of Aβ. In addition, PE with albu-
min replacement could restore the antioxidant capacity of
plasma albumin which is reduced in AD22,24-26 and facili-
tate the removal of other potentially harmful metabolites
(eg, autoantibodies, alloantibodies, and toxins).23,27
The AMBAR study, which was preceded by a pilot28
and a phase 2 studies,29,30 was the first study to utilize PE
in a phase 2b/3 trial in the patients with AD. Primary and
secondary clinical results of the AMBAR study, which
have been previously reported,31,32 demonstrated that PE
slowed the decline, stabilized or even improved the disease
symptoms as assessed by cognitive, neuropsychological,
global assessment, and neuropsychiatric test scales.
Given the lack of experience with the application of
PE in elderly patients with cognitive decline such as AD,
the focus of this study is on the unique application of PE
modalities in the patients with AD, including the use of a
new low-volume plasma exchange (LVPE) technique as
well as of sham PE procedures.
2 | MATERIAL A ND METHODS
2.1 | Regulatory compliance
The prospective, randomized, controlled AMBAR trial was
conducted at 41 sites in Spain and the United States. This
study was conducted in accordance with applicable regula-
tory guidelines and the International Council for
BOADA ET AL.
F I G U R E 1 Outline of treatment
periods and distribution of treatment
groups in the AMBAR study.
IVIG, intravenous immunoglobulin;
LVPE, low-volume plasma exchange;
TPE, therapeutic plasma exchange
Harmonization of Technical Requirements for Pharma-
ceuticals for Human Use, and Good Clinical Practice. The
protocol, the informed consent form, and the patient infor-
mation sheets were approved by Institutional Review
Boards or Ethics Committees from the sites and the
Health Authorities in Spain and the United States. The
informed consent was obtained from each patient or their
qualified representative prior to enrollment in the study.
2.2 | Patient selection
The “safety population” (ie, all patients included in the
study and subjected to at least one PE session)31 consisted
of 322 patients (54% women and 46% men), average age
of 69.0 ± 7.7 years, with a diagnosis of mild-to-moderate
AD (by National Institute of Neurological and Communi-
cation Disorders and Stroke-Alzheimer's Disease and
Related Disorders Association criteria) and had an aver-
age Mini-Mental State Examination score of 21.6 ± 2.6.
Details on demographic and clinical characteristics of
patients as well as full inclusion and exclusion criteria
are available in the primary paper31 and summarized in
Table SI.
2.3 | Treatment groups
Enrolled patients were randomly assigned to one of four
groups (1:1:1:1). PE with albumin (Albutein 5%, Grifols)
replacement for the intensive phase and PE with albumin
(Albutein 20%, Grifols) replacement for the maintenance
phase was administered in two different doses (“low” and
“high” albumin), to three of the groups. Two of the PE
groups also received IVIG (Flebogamma 5% DIF, Grifols,
Barcelona, Spain). A simulated noninvasive PE procedure
(“sham”) that did not involve any fluid transfer was per-
formed on the placebo group (details below).
47
The treatment period in the AMBAR study was
14 months. Weekly PE was performed for 6 weeks in the
treatment groups during a therapeutic plasma exchange
(TPE) treatment period, followed by a 12-month period
of monthly LVPE treatments.15,31 Figure 1 summarizes
the treatment periods and the distribution of patients in
the treatment groups.
2.4 | Conventional (therapeutic) PE
treatment
A commercial continuous flow cell separator was used for
TPE. During the TPE treatments, approximately one
plasma volume (2500-3000 mL of plasma or 35-45 mL/kg
based on height, weight, and hematocrit) was removed and
replaced by an equal volume of 5% albumin (125-150 g)
under continuous flow. Each session was carried out at an
infusion rate of 60-100 mL/min. An infusion typically
started at a low rate, and was increased as tolerated.
2.5 | LVPE treatment
For LVPE, a prototype modified from commercial plasma
donation devices (Autopheresis-C; Fenwal, Lake Zurich, IL
or Aurora; Fresenius Kabi, Bad Homburg, Germany) devel-
oped by Fresenius Kabi and Grifols was used. Further
information on LVPE devices is provided in the “LVPE
devices” section of the Supporting Information Material.
Central or peripheral venous access for TPE was cho-
sen by the personnel at the study sites based on their
practice. When chosen, placement and verification of
central venous access was performed according to exist-
ing standard procedures at the study site. All LVPE pro-
cedures were performed via peripheral venous access.15,31
LVPE differs from routine plasmapheresis (plasma
donation) only in that there is the replacement of
48 BOADA ET AL.

F I G U R E 2 Preparation of sham central venous catheter assembly used in sham therapeutic plasma exchange (TPE). A, Shown is the
hydrocolloid patch on pediatric urostomy bag prior to removal of the bag. B, Shown are the bevel cut on the catheter tip and the point of
insertion through the ostomy patch. C, Central venous catheter assembly has been inserted through the ostomy patch and sutured in
place. D, Sham central venous catheter completed with dressings in place

removed plasma with albumin or IVIG, hence PE. In
contrast to TPE, in the LVPE treatments the flow was dis-
continuous: first, 690-880 mL of plasma (using a plasma
donation nomogram based on weight, see Table SII) were
removed, and afterwards it was replaced with 100 to
200 mL 20% albumin (20 g albumin = “low-albumin”
and 40 g albumin = “high-albumin”). This plasma vol-
ume is similar to that removed during a routine plasma-
pheresis. Participating centers could decide to administer
saline solution after LVPE to prevent hypovolemia and
blood pressure-related adverse events (AEs) caused by
the discontinuity between cell separation and albumin
infusion.
In two of the groups (“low-albumin + IVIG” and
“high-albumin + IVIG”), the albumin infusions were
alternated with IVIG (10 g IVIG = “low IVIG” or 20 g
IVIG = “high IVIG”) every 4 months during the LVPE
period15,31 (see Figure 1). Albumin dosage was adjusted
based on the volume of plasma removed while IVIG
doses were fixed (Table SII).
2.6 | Sham PE treatment
Patients in the placebo group were given sham treat-
ments at the same time points as PE was performed in
the active treatment groups (Figure 1). Sham treatments
were designed to simulate PE as realistically as possible
to maintain patient blinding (Figure 2). No plasma was
removed and no albumin or IVIG was administered dur-
ing sham treatments. Further information on sham treat-
ment is provided in the “Sham PE treatment” section of
the Supporting Information Material.
2.7 | Safety assessments and analysis
The primary safety assessment was the percent of TPE
(including consideration to venous access: central vs
peripheral) and LVPE procedures associated with at
least one AE related to the study procedure. AEs with
an onset ≤72 h after the end of a PE procedure were
BOADA ET AL.
TABLE 1 Patient disposition by plasma exchange treatment assignment
Placebo Low-albumin
Randomized, n 87 82
Did not receive study product, n 7 4
Full analysis set, n 80 78
Received wrong treatment, n –1 0 0
Safety analysis set, n 79 78
Completed study, n (%)a 64 (80.0) 61 (78.2)
Abbreviation: IVIG, intravenous immunoglobulin.
a
Percentage referred to full analysis set.
considered related to procedure. In addition, the per-
centage of TPE and LVPE procedures associated with
an AE that was or was not related to the PE procedure
was assessed.
Statistics were descriptive, and included frequencies
and percentages for categorical variables, and means,
medians, and/or ranges for continuous variables.
3 | R E SUL T S
3.1 | Study and procedure completion
rates
The distribution of enrolled patients into the four groups
is shown in Table 1. One patient randomized to placebo
group received inadvertently a real central venous cathe-
ter. The patient was then included in the high-
albumin + IVIG group but analyzed in the placebo group
for efficacy analysis and considered as a treated patient
for safety analysis. A total of 4709 PE procedures were
performed (3486 real; 1223 sham). TPE made up 1283 of
the active treatments and 2203 were LVPE.
3.2 | PE procedure characteristics
Elapsed time for the TPE procedures were similar across all
treatment groups for the first treatment (approximately
110 min) and was shortened slightly over the course of the
TPE procedures (96.1-107.8 min for last TPE). The duration
of the sham procedure was shorter than the TPE (approxi-
mately 60 min vs approximately 100-110 min).
When the number of planned PE procedures com-
pleted was examined over the course of the study, the
percentage of procedures completed was highest in the
placebo and low-albumin groups (79.7% and 79.5%,
respectively) compared with the groups that included
49
Low-albumin + IVIG High-albumin + IVIG Total
92 86 347
6 8 25
86 78 322
1 0
86 79 322
56 (65.1) 51 (65.4) 232 (72.0)
IVIG treatment: 64.0% for low-albumin + IVIG and
67.1% for the high-albumin + IVIG group.
The volume of PE during the six TPE procedures was
very similar across procedures and across active treat-
ment groups: from 2385.6 ± 68.7 to 2674.4 ± 63.7 mL
(mean ± SE). The plasma volume exchanged was also
similar across the active treatment groups during the
12 LVPE procedures: from 719.9 ± 22.1 to 885.0
± 163.7 mL.
3.3 | All AEs (regardless of relationship
to procedure)
When all AEs within 72 h of PE were assessed for all PE
procedures, the percentage of PE affected with any AE
ranged from 4.1% in the placebo group to 18.8% in the
high-albumin + IVIG group. The low-albumin group had
AEs in 16.4% of the procedures, similar to the low-
albumin + IVIG group (15.7%).
When all AEs were summarized (regardless of tim-
ing), AEs were found to be more common in the active
treatment groups than in the placebo group (90.1% vs
70.9%, respectively, of patients reported at least 1 AE dur-
ing the study).
3.4 | Procedure-related AEs
Out of the 4709 total PE procedures, 501 (10.6%) were
associated with 637 procedure-related AEs within the
72 h after procedure completion. The percentage of pro-
cedures associated with at least one AE was higher for
the TPE procedures (16.9%) than for the LVPE proce-
dures (12.5%).
The rate of procedures with at least one AE was similar
in all the active treatment groups: 13.5% for the low-
albumin group, 12.5% for the low-albumin + IVIG group
50 BOADA ET AL.

F I G U R E 3 Adverse events (AEs) over the course of the study by treatment group. IVIG, intravenous immunoglobulin; LVPE,
low-volume plasma exchange; TPE, therapeutic plasma exchange period

T A B L E 2 Number of procedure-related adverse events for all therapeutic plasma exchange procedures in central versus peripheral
venous access by treatment group

Placebo Low-albumin Low-albumin + IVIG High-albumin + IVIG All PE-treated

Central access
N 208 259 241 196 696
TPE with at least 1 AE, n (%) 3 (1.4) 59 (22.8) 38 (15.8) 43 (21.9) 140 (20.1)
Peripheral access
N 227 171 207 209 587
TPE with at least 1 AE, n (%) 2 (0.9) 16 (9.4) 30 (14.5) 31 (14.8) 77 (13.1)

Abbreviations: AE, adverse event; IVIG, intravenous immunoglobulin; TPE, therapeutic plasma exchange.

and 16.5% for the high-albumin + IVIG group. Conversely,
for the placebo (sham treatment) group the rate was 0.7%.
3.5 | TPE vs LVPE-related AEs
When procedure-related AEs were broken down into
TPE and LVPE treatments, the pattern was the same as
that seen for all PE procedures. For TPE procedures the
incidence of procedures with at least one associated AEs
was as follows: placebo 1.1%; low-albumin 17.4%, low-
albumin + IVIG 15.2%, and high-albumin + IVIG
18.3%. For the LVPE procedures, procedures with at
least one associated AEs were similarly low in the pla-
cebo group (0.5%) and higher in the active treatment
groups: low-albumin 11.3%; low-albumin + IVIG 10.9%,
and high-albumin + IVIG 15.4%. These results are sum-
marized in Figure 3. AEs frequency was distinctly
higher during the TPE phase of the study compared to
the LVPE phase.
The most frequently reported types (MedDRA Pre-
ferred Term) of procedure-related AEs based on numbers
(% of PE with at least 1 related AE) of TPE or LVPE were:
General Disorders and Administration Site Conditions
(4.2% and 2.8%, respectively; mainly catheter- and injec-
tion site-related AEs), nervous system disorders (3.5%
and 2.6%, respectively; mainly dizziness, paresthesia, and
presyncope), and Vascular Disorders (2.5% and 4.4%,
respectively; mainly hypotension). Further details are
provided in Table SIII.
3.6 | Central vs peripheral access-
related AEs
The percentage of TPE procedures with at least one
procedure-related AE was calculated for central and
peripheral venous access (Table 2). Percentage of proce-
dures with at least one AE was higher with central access
compared to peripheral access in all three active treat-
ment groups (20.1% vs 13.1%, respectively). The incidence
of procedures with at least one associated AE in the pla-
cebo group was very low (1.4% central and 0.9%
peripheral).
BOADA ET AL.
The most frequently reported types (MedDRA Pre-
ferred Term) of procedure-related AEs based on numbers
(% of PE with at least 1 related AE) of TPE with central
access were general disorders and administration site
conditions (6.0%, mainly catheter site erythema), and
nervous system disorders (4.7%, mainly dizziness, pares-
thesia, and syncope). In TPE with peripheral access, no
AE category stand out over others. Further details are
provided in Table SIV.
4 | DISCUSSION
PE has been used safely in multiple neurological disor-
ders, such as severe acute inflammatory demyelinating
polyneuropathy, Guillain-Barré syndrome, multiple scle-
rosis, and others.23,33-38 PE is a well-studied procedure
and AEs could theoretically be anticipated based on clini-
cal experience and the existing information on the safety
profile of the administered products, albumin and IVIG,
used in the AMBAR trial.39,40 However, PE had never
been tested in AD, typically an aged patient population
with associated health issues.
The basic safety analysis of the AMBAR trial previ-
ously reported that 90% of the PE procedures were
uneventful,31 as expected based on the safety profile for
PE previously reported.37,41-43 The high percentage
of finalized procedures and the relatively low incidence
of AEs highlighted the feasibility and safety, respectively,
of this procedure in mild-to-moderate AD patients. Here
we extended the safety analysis emphasizing the proce-
dure type (TPE vs LVPE), the different PE treatment
modalities (albumin doses; with/without IVIG) and TPE
venous access (central vs peripheral).
The large number of proven and potential therapeutic
indications for PE can be interpreted that the procedure
is generally considered safe. This has been substantiated
in multiple studies.44-47 Similar to the results of the pre-
sent study, Guptill et al. found a low rate of serious com-
plications with PE and a greater frequency of AEs with
central access when compared to peripheral access.46
When the safety of PE was studied in a geriatric popula-
tion and compared to a nongeriatric population, it was
determined that frequency and nature of AEs were simi-
lar.45 These results agree with the current study, in that
TPE was found to be a safe and tolerable procedure even
in elderly populations with serious medical conditions.
In the current study, the safety and utility of LVPE, a
new PE modality based on conventional plasma dona-
tion, was also demonstrated. The low incidence of AEs
with the LVPE procedures in this study agrees with pub-
lished literature on the safety of plasma donation. Plasma
51
donation is a very common and well-tolerated procedure
with an estimated 48.7 million donations occurring in the
United States in 2018.48 The relative safety of these dona-
tions is indicated by the previously described studies and
by data from the U.S. Food and Drug Administration.
Studies of AEs associated with plasma donation have
shown that these events are very rare.49,50
Some of the most common AEs previously reported in
the primary results of the AMBAR study were clearly
related to the procedure itself: extravasation and injection
site reactions.31 However, some of the other AEs have been
reported as associated with the administration of the
replacement fluids—albumin and IVIG. Hypotension is
one of the most common side effects reported after admin-
istration of albumin.51 Hypotension has been reported with
IVIG as well.52 The higher incidence of hypotension in the
LVPE can be ascribed to the discontinuity between cell sep-
aration and albumin infusion in the procedure. Injection
site reactions and dizziness have been also previously
reported in the primary results of the AMBAR study31 and
after IVIG administration.52 The higher incidence of AEs in
the treatment groups that received albumin and IVIG may
account for the higher withdrawal rate in these groups.
When overall AEs (related and unrelated to proce-
dures) were considered, the number of patients with AEs
reported in the placebo group was 69.6%. This suggests
that the overall population in this study had underlying
health issues. In fact, medical records taken at baseline
before treatment inception showed that 98.8% of the
overall patient population reported relevant medical
conditions,31 which could account for the number of
nonprocedure-related AEs in the study.
Limitations of the AMBAR trial include that AD
patients were diagnosed based on the clinical phenotype
rather than on biomarkers, as well as a possible imperfec-
tion of the blinding procedure, in addition to the shorter
time allotted for the placebo procedure compared to the
elapsed time for the actual procedure in treated groups.
However, the low consent withdrawal rate observed in
the placebo group suggest that blinding was effective.
5 | CONCLUSION
Overall, PE using albumin with or without IVIG was fea-
sible and well-tolerated by AD patients, which are typi-
cally an elderly population with associated health issues.
Frequency and nature of procedure-related AEs were
similar to those observed in other PE-treated diseases.
The large number of successful TPE + LVPE procedures
conducted in this specific population suggests that PE
could be a viable therapeutic approach to treat AD.
52
A C K N O WL E D G M E N T S
The authors thank patients for their indispensable contribu-
tion. Jordi Bozzo PhD, CMPP and Michael K James, PhD
(Grifols) are acknowledged for medical writing and edito-
rial support in the preparation of this manuscript. The
AMBAR study is funded by Grifols, a manufacturer of ther-
apeutic human serum albumin and intravenous immune
globulin.
CONFLICT OF INTEREST
Mercè Boada has been a consultant for Araclon, Avid,
Bayer, Elan, Grifols, Janssen/Pfizer, Lilly, Neuroptix,
Nutricia, Roche, Sanofi, Biogen, and Servier; and received
fees for lectures and funds for research from Araclon,
Esteve, Grifols, Janssen, Novartis, Nutricia, Piramal,
Pfizer-Wyett, Roche, and Servier. Oscar L. L
opez has
been a consultant for Grifols and Lundbeck. Laura
Núñez, Miquel Barcel
o, Carlota Grifols, and Antonio
P
aez are full-time employees of Grifols. Zbigniew
M. Szczepiorkowski has been on the board of directors or
an advisory committee for, ICCBBA, Fenwal/Fresenius
Kabi, Grifols, and Novartis; and has received grants
and/or contract research for Fresenius Kabi, Erydel, Cell-
phire, and Cytosorbents. Javier Olazar
an has been a con-
sultant for Schwabe and Grifols; and received fees for
lectures and funds for research from Esteve, Grifols,
Nutricia, and Neuraxpharm. Other authors declare no
conflict of interest.
DATA AVAILABILITY STATEMENT
The data that support the findings of this study are avail-
able from the corresponding author upon reasonable
request.
E TH IC S ST A T EME N T S
Institutional Review Boards or Ethics Committees from
the sites and the health authorities approved the proto-
col, the patient information sheets, and the informed
consent form, in agreement with the Declaration of Hel-
sinki as well as the standards of Good Clinical Practice.
ORCID
Antonio P

aez https://orcid.org/0000-0003-1756-4534
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Additional supporting information can be found online
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BOADA ET AL.
How to cite this article: Boada M, Kiprov D,
Anaya F, et al. Feasibility, safety, and tolerability of
two modalities of plasma exchange with albumin
replacement to treat elderly patients with
Alzheimer's disease in the AMBAR study. J Clin
Apher. 2023;38(1):45‐54. doi:10.1002/jca.22026